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Mendeliome v0.4533 IBA57 Zornitza Stark Phenotypes for gene: IBA57 were changed from Multiple mitochondrial dysfunctions syndrome 3, MIM#615330 to Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4531 IBA57 Zornitza Stark changed review comment from: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.; to: MMDS3: More than 15 families reported with bi-allelic variants in this gene and a severe neurodegenerative disorder characterised by loss of previously acquired developmental milestones in the first months or years of life. Some affected individuals have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some individuals die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some individuals may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable.

SPG74: Three families with spastic paraparesis as a feature of the condition.
Mendeliome v0.4531 IBA57 Zornitza Stark edited their review of gene: IBA57: Changed phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330, Spastic paraplegia 74, autosomal recessive MIM#616451
Mendeliome v0.4529 IBA57 Zornitza Stark Mode of inheritance for gene: IBA57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 IBA57 Zornitza Stark reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: None; Publications: 23462291, 25971455, 27785568, 28671726, 28913435; Phenotypes: Multiple mitochondrial dysfunctions syndrome 3, MIM#615330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4528 RP1L1 Teresa Zhao reviewed gene: RP1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23281133, 30025130, 32360662; Phenotypes: Occult macular dystrophy (MIM#613587) AD, Retinitis pigmentosa 88 (MIM#618826) AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4528 CYP11B2 Paul De Fazio reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8439335, 9360501, 15240589, 9814506, 12788848, 8772616; Phenotypes: Hypoaldosteronism, congenital, due to CMO I deficiency (MIM#203400) or due to CMO II deficiency (MIM#610600).; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4525 LIFR Zornitza Stark edited their review of gene: LIFR: Added comment: Bi-allelic variants: At least 28 unique variants (nonsense, frameshift, splicing, missense, gross deletions) have been reported in individuals with Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, 22 of which are predicted to cause LOF, suggesting homozygous LOF is the mechanism of disease for this gene. Variants in this gene have been reported in at least 22 probands in four publications.

Mono-allelic variants: associated with CAKUT in 4 individuals, mouse model recapitulates phenotype.; Changed rating: GREEN; Changed publications: 14740318, 20447141, 24988918, 29620724, 28334964; Changed phenotypes: Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome, MIM# 601559, CAKUT; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4523 PAX7 Zornitza Stark Mode of inheritance for gene: PAX7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 PAX7 Zornitza Stark reviewed gene: PAX7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31092906, 11030621, 24065826, 31092906, 8631261, 11030621, 24065826; Phenotypes: Myopathy, congenital, progressive, with scoliosis, MIM# 618578; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4522 MADD Zornitza Stark Phenotypes for gene: MADD were changed from Intellectual disability; seizures; autonomic dysfunction; endocrine dysfunction to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Mendeliome v0.4521 MADD Zornitza Stark edited their review of gene: MADD: Added comment: OMIM have assigned two disease entities to this gene.

DEEAH syndrome: 12 families.
NEDDISH syndrome: 8 families.; Changed phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Mendeliome v0.4520 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Added comment: Monoallelic :
DD/ID was a feature in >= 6 individuals with monoallelic de novo SLC12A2. An individual with an exon 22 truncating variant was reported to have normal milestones and cognitive function. Exon 21 variants have been described in individuals with rather isolated hearing impairment (possibly some associated motor delay, but normal cognition). Hearing impairment was also reported in 2/6 patients with variants in other exons (1 missense / 1 frameshift).

Biallelic :
DD/ID was reported in at least 3 individuals in literature. Hearing impairment has been reported on 2 occasions (although this was not probably evaluated in all subjects).

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Monoallelic SLC12A2 mutations :

► Individuals with de novo mutations and developmental disorder were first identified by the DDD study (2017 - PMID: 28135719). 5 of them have been reported in detail by McNeill et al (below).

► McNeill et al (2020 - PMID: 32658972) report on 6 individuals with neurodevelopmental disorder due to de novo SLC12A2 mutation. All presented DD or ID ranging from mild to severe. ASD was reported in 3/6. Sensorineural hearing loss was a feature in 2/6 with the remaining having normal formal evaluations. Brain, cardiac and/or additional malformations were reported in a single individual. Following non-diagnostic prior work-up (CMA, FMR1 or other investigations) trio exome sequencing revealed missense (4/6) or truncating variants (2/6).

Three additional individuals (incl. a father and his son) with missense variants in exon 21 (NM_001046.3 / p.Glu979Lys and p.Glu980Lys) presented with bilateral sensorineural hearing loss. Speech and/or motor delay reported in these cases were attributed to the hearing impairment/vestibular arreflexia (cognitive abilities not tested).

SLC12A2 encodes sodium-potassium-chloride transporter 1 (also NKCC1).

The GTEx project has identified 8 isoforms. In brain both exon 21-containing/deleted isoforms are expressed (cited Morita et al 2014 - PMID: 24695712). As the authors discuss, RNA-seq of the developing mouse cochlea suggests that the exon 21 containing isoform is the single transcript expressed. Evidence from RNA-seq data (BrainSpan project) and literature suggests that the significant amounts of exon 21 lacking isoforms in fetal brain compensate for the deleterious effects of exon 21 variants and explain the lack of NDD in relevant patients.

Slc12a2 (NKCC1) null mouse model has demonstrated that the transporter plays a role in accumulation of the potassium rich endolymph in the inner ear, with NKCC1 absence causing sensorineural deafness and imbalance. Slc12a2 display cochlear malformations, loss of hair cells and hearing impairment (cited Delpire et al 1999 - PMID: 10369265). The brain phenotype has not been studied extensively, although loss of Slc12a2 has been shown to inhibit neurogenesis (cited: Magalhães and Rivera et al. - PMID: 27582690).

Slc12a2 null zebrafish display a collapse of the otic vesicle and reduced endolymph (Abbas and Whitfield, 2009 - PMID: 19633174) relevant to the human hearing disorder.

In vitro assessment of NKCC1 ion transporter function in Xenopus laevis, supported the deleterious effect of the identified variants (significant reduction in K+ influx). Using available single cell RNA-seq data the authors further demonstrated that SLC12A2 expressing cells display transcriptomic profiles reflective of active neurogenesis.

► Delpire et al (2016 - PMID: 27900370 - not reviewed in detail) described a 13 y.o. girl harboring a de novo 11-bp deletion in SLC12A2 exon 22. This individual reached developmental milestones on time and had a NORMAL cognitive function. Hearing was seemingly normal. Features included orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency and multiorgan failure incl. gut and bladder. Exome in the proband, parents and 3 unaffected sibs suggested SLC12A2 as the only candidate for her phenotype. Functional analyses in Xenopus laevis oocytes suggested that a non functional transporter was expressed and trafficked to the membrane as the wt. Detection of the truncated protein at higher molecular sizes suggested either enhanced dimerization or misfolded aggregate. There was no dominant-negative effect of mutant NKCC1. In patient fibroblasts a reduced total and NKCC1-mediated K+ influx.

► Mutai et al (2020 - PMID: 32294086) report on several individuals from 4 families, harboring variants within exon 21 or - in one case - at it's 3' splice-site (leading to skipping oe this exon at the mRNA level). All subjects were investigated for severe/profound hearing loss (in line with the role of exon 21-included isoforms in cochlea. The variant segregated with hearing impairment in 3 generations of a family while in all other subjects the variant had occured as de novo event. Despite motor delays (e.g. the subject from fam2 could not hold head or sit at the age of 10m / the proband in Fam3 was able to hold his head and walk at 6 and 20 m respectively) behavior and cognition were commented to be within normal range.


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Biallelic SLC12A2 mutations:

► Anazi et al (2017 - PMID: 29288388) briefly reported on a 3 y.o. boy (17DG0776) with central hypotonia, neonatal respiratory distress, failure to thrive, global DD and microcephaly and a skeletal survey suggestive of osteopenia. After non-diagnostic prior investigations (CMA revealing a 1p duplication classified as VUS, extensive metabolic workup), WES revealed a homozygous SLC12A2 splicing variant [NM_001046.2:c.2617-2A>G].

► Macnamara et al (2019 - PMID: 30740830) described a 5.5 y.o. male with sensorineural hearing loss, profound delays in all developmental areas among several other features (choanal atresia, failure to thrive, respiratory problems, absent sweat and tear production or salivation, GI abnormalities). Genetic testing for several disorders considered (cystic fibrosis, spinal muscular atrophy, sequencing and del/dup analysis of mtDNA) was normal. CMA revealed paternal uniparental isodisomy for chr. 5 and WGS a homozygous 22kb deletion in SLC12A2. This was followed by confirmation of homozygosity in the proband, heterozygosity of the unaffected father, delineation of breakpoints (chr5:127441491-127471419). mRNA studies in patient fibroblasts confirmed deletion of ex2-7, splicing of ex1 directly to ex8 and introduction of a premature stop codon in ex9. qRT-PCR confirmed that mRNA is likely subjected to NMD (expression ~80% of control). Western blot confirmed absence of the protein in the patient's fibroblasts. Again mouse models are thought to recapitulate the hearing defect but also the deficient saliva production (cited Evans et al 2000 - PMID: 10831596). Again the authors speculate a role of SLC12A2 in brain development based on evidence from murine models (migration, dendritic growth, increse in neuron density through regulation of GABAergic signalling (Young et al 2012 - PMID: 23015452). Hypotheses are also made on a regulatory relationship between NKCC1 and CFTR based on mRNA data from the ko mouse model.

► Stödberg et al (2020 - PMID: 32754646) reported 2 sibs with a complex neurodevelopmental disorder due to compound heterozygosity for a frameshift SLC12A2 variant and a splicing one (NM_001046:c.1431delT and c.2006-1G>A). Both presented hypotonia, neonatal S. aureus parotitis and respiratory problems (incl. apneas). While the older sib died at the age of 22 days, the younger one had persistent respiratory issues incl. a dry respiratory mucosa motivating metabolic, immunology investigations and testing for CF. She displayed microcephaly (OFC -2.5 SD, H was also -3.5SD), severe intellectual disability. MRI was suggestive of white matter and basal ganglia abnormalities. Other features incl. hearing impairment, and lack of tears,saliva and sweat, constipation and intestinal malrotation. There was facial dysmorphism. The variants were the only retained following WGS of the 2 affected sisters, parents and an unaffected brother. The splicing variant was shown to result in skipping of exon 13, while the indel in NMD. Again the authors discuss that the deficient saliva production, impaired hearing and GI problems are recapitulated in the mouse model (several refs provided).; Changed rating: GREEN; Changed publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Changed phenotypes: Kilquist syndrome, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4520 VPS37A Zornitza Stark Phenotypes for gene: VPS37A were changed from to Spastic paraplegia 53, autosomal recessive, MIM# 614898
Mendeliome v0.4518 VPS37A Zornitza Stark Mode of inheritance for gene: VPS37A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4516 VPS37A Zornitza Stark reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, MIM# 614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4516 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from to Spastic paraplegia 49, autosomal recessive, MIM# 615031; Autonomic-sensory neuropathy
Mendeliome v0.4514 TECPR2 Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4513 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, MIM# 615031, Autonomic-sensory neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4511 SMOC2 Zornitza Stark Mode of inheritance for gene: SMOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 SMOC2 Zornitza Stark reviewed gene: SMOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152679, 23317772, 32908163; Phenotypes: Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 MAG Zornitza Stark Phenotypes for gene: MAG were changed from to Spastic paraplegia 75, autosomal recessive, MIM# 616680
Mendeliome v0.4508 MAG Zornitza Stark Mode of inheritance for gene: MAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4507 MAG Zornitza Stark reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 26179919, 31402626, 32629324; Phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4507 DSTYK Zornitza Stark Phenotypes for gene: DSTYK were changed from to Congenital anomalies of kidney and urinary tract 1, MIM# 610805; Spastic paraplegia 23, MIM# 270750
Mendeliome v0.4505 DSTYK Zornitza Stark Mode of inheritance for gene: DSTYK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4504 DSTYK Zornitza Stark reviewed gene: DSTYK: Rating: GREEN; Mode of pathogenicity: None; Publications: 23862974, 23862974, 28618409, 28157540, 23862974; Phenotypes: Congenital anomalies of kidney and urinary tract 1, MIM# 610805, Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4503 ZMYM2 Zornitza Stark gene: ZMYM2 was added
gene: ZMYM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to 32891193
Phenotypes for gene: ZMYM2 were set to Congenital anomalies of kidney and urinary tract; Neurodevelopmental disorder
Review for gene: ZMYM2 was set to GREEN
Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features.

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Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants.

Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly.

14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family.

The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT.

ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body).

It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors.

The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT).
Sources: Literature
Mendeliome v0.4501 MTX2 Zornitza Stark gene: MTX2 was added
gene: MTX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTX2 were set to 32917887
Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Review for gene: MTX2 was set to GREEN
Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation.
Sources: Literature
Mendeliome v0.4500 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Mendeliome. Sources: Literature
SV/CNV tags were added to gene: RREB1.
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917
Phenotypes for gene: RREB1 were set to Noonan syndrome-like disorder
Review for gene: RREB1 was set to RED
Added comment: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes.

In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.
Sources: Literature
Mendeliome v0.4497 NEMF Zornitza Stark gene: NEMF was added
gene: NEMF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEMF were set to 32934225
Phenotypes for gene: NEMF were set to Intellectual disability; neuropathy
Review for gene: NEMF was set to GREEN
Added comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature
Mendeliome v0.4496 FNIP1 Arina Puzriakova gene: FNIP1 was added
gene: FNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FNIP1 were set to 32181500; 32905580
Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia
Review for gene: FNIP1 was set to GREEN
Added comment: - PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.

- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway.
Sources: Literature
Mendeliome v0.4494 TAOK1 Zornitza Stark Mode of inheritance for gene: TAOK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4493 TAOK1 Zornitza Stark reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230721; Phenotypes: TAOK1-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4493 CSF1R Zornitza Stark Phenotypes for gene: CSF1R were changed from to Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476); Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820)
Mendeliome v0.4490 CSF1R Zornitza Stark Mode of inheritance for gene: CSF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4489 TAOK1 Elena Savva reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31230721; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4487 L2HGDH Zornitza Stark Mode of inheritance for gene: L2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4486 L2HGDH Zornitza Stark reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15385440; Phenotypes: L-2-hydroxyglutaric aciduria, MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4486 CSF1R Elena Savva reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31330095, 24336230; Phenotypes: Brain abnormalities, neurodegeneration, and dysosteosclerosis, (MIM#618476), Leukoencephalopathy, diffuse hereditary, with spheroids, (MIM#221820); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4486 LMNB1 Zornitza Stark Mode of inheritance for gene: LMNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4483 LMNB1 Zornitza Stark Phenotypes for gene: LMNB1 were changed from to Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500
Mendeliome v0.4482 LMNB1 Zornitza Stark reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32910914, 16951681, 19151023; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis, Leukodystrophy, adult-onset, autosomal dominant, MIM#169500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4482 L2HGDH Elena Savva reviewed gene: L2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20052767; Phenotypes: L-2-hydroxyglutaric aciduria MIM#236792; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4482 MAPK8 Zornitza Stark reviewed gene: MAPK8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31784499; Phenotypes: Chronic mucocutaneous candidiasis, Connective tissue disorders; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4480 MAPK8 Arina Puzriakova gene: MAPK8 was added
gene: MAPK8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPK8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8 were set to 31784499
Phenotypes for gene: MAPK8 were set to Chronic mucocutaneous candidiasis; Connective tissue disorders
Added comment: PMID: 31784499 (2020) - Three cases in a single family with chronic mucocutaneous candidiasis and a connective tissue disorder that clinically overlaps with hEDS. WES revealed a splice-site variant (c.311+1G>A) in the MAPK8 gene that segregated with the disorder. Includes supportive functional data using patient-derived fibroblasts, showing that the variant impairs IL-17A/F immunity and the development of Th17 cells.
Sources: Literature
Mendeliome v0.4480 CTNNBL1 Arina Puzriakova gene: CTNNBL1 was added
gene: CTNNBL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CTNNBL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNBL1 were set to 32484799
Phenotypes for gene: CTNNBL1 were set to Primary Immunodeficiency; Autoimmune Cytopenias; Common variable immunodeficiency
Added comment: PMID: 32484799 (2020) - One patient with common variable immunodeficiency associated with autoimmune cytopenia (CVID+AIC), associated with a homozygous missense M466V variant in the CTNNBL1 gene. Functional studies showed that the variant impaired interaction with AID, in turn disrupting AID-mediated antibody diversification in activated B-cells.
Sources: Literature
Mendeliome v0.4476 TNNI2 Zornitza Stark Mode of inheritance for gene: TNNI2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4475 MEIS2 Michelle Torres reviewed gene: MEIS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25712757; Phenotypes: Cleft palate, cardiac defects, and mental retardation (MIM#600987); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4475 TNNI2 Michelle Torres reviewed gene: TNNI2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 17194691, 25340332; Phenotypes: Arthrogryposis, distal, type 2B1 (MIM#601680); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4473 TAF2 Elena Savva reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24084144, 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4471 VPS11 Zornitza Stark Mode of inheritance for gene: VPS11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4470 VPS11 Zornitza Stark reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120463, 26307567, 27473128; Phenotypes: Leukodystrophy, hypomyelinating, 12, MIM# 616683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4468 GGT1 Zornitza Stark Mode of inheritance for gene: GGT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4466 GGT1 Elena Savva edited their review of gene: GGT1: Added comment: PMID: 29483667 - 1 family (2 sibs) w/ a homozygous 16.9kb deletion spanning part of the gene and no others. Carrier parents were normal.

PMID: 23615310 - homozygous mutant mouse model have dwarfism, cataracts and coat colour abnormalities. Protein activity reduced to 4% of wildtype. Noted it was for use as a GGT deficiency model.

PMID: 31520399 - 2 families with AD inheritance showing GGT1 deficiency but NO clinical symptoms. Authors call GGTemia a benign condition.; Changed publications: PMID: 29483667, 23615310, 31520399
Mendeliome v0.4464 NAXE Zornitza Stark Mode of inheritance for gene: NAXE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4463 NAXE Zornitza Stark changed review comment from: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.; to: Early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.
Mendeliome v0.4463 NAXE Zornitza Stark reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27122014, 27616477, 31758406; Phenotypes: Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4461 NAXD Zornitza Stark Mode of inheritance for gene: NAXD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4460 NAXD Zornitza Stark reviewed gene: NAXD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30576410, 31755961, 32462209; Phenotypes: Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4458 ISCA2 Zornitza Stark Mode of inheritance for gene: ISCA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4457 ISCA2 Zornitza Stark reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25539947, 29297947, 29122497, 29359243; Phenotypes: Multiple mitochondrial dysfunctions syndrome 4, MIM# 616370; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4457 PRIMPOL Zornitza Stark Phenotypes for gene: PRIMPOL were changed from to Myopia 22, autosomal dominant, MIM# 615420
Mendeliome v0.4455 PRIMPOL Zornitza Stark Mode of inheritance for gene: PRIMPOL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4453 PRIMPOL Zornitza Stark reviewed gene: PRIMPOL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopia 22, autosomal dominant, MIM# 615420; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4453 PRIMPOL Teresa Zhao reviewed gene: PRIMPOL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23579484, 25262353, 27230014, 32375772; Phenotypes: Myopia 22 (MIM#615420) AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4452 KCNN4 Zornitza Stark gene: KCNN4 was added
gene: KCNN4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KCNN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN4 were set to 26148990; 26198474; 26178367
Phenotypes for gene: KCNN4 were set to Dehydrated hereditary stomatocytosis 2, MIM# 616689
Review for gene: KCNN4 was set to GREEN
Added comment: At least three families reported.
Sources: Expert list
Mendeliome v0.4450 C15orf41 Zornitza Stark gene: C15orf41 was added
gene: C15orf41 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C15orf41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C15orf41 were set to 23716552; 32293259; 31191338; 29885034
Phenotypes for gene: C15orf41 were set to Dyserythropoietic anemia, congenital, type Ib, MIM# 615631
Review for gene: C15orf41 was set to GREEN
Added comment: At least 6 families reported, functional data.
Sources: Expert list
Mendeliome v0.4447 XRCC2 Zornitza Stark Mode of inheritance for gene: XRCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4445 XRCC2 Zornitza Stark reviewed gene: XRCC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208205, 22232082, 11118202; Phenotypes: Fanconi anemia, complementation group U, MIM# 617247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4443 TSR2 Zornitza Stark Mode of inheritance for gene: TSR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4441 TSR2 Zornitza Stark reviewed gene: TSR2: Rating: RED; Mode of pathogenicity: None; Publications: 24942156; Phenotypes: Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, MIM# 300946; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4439 SRP72 Zornitza Stark Mode of inheritance for gene: SRP72 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4437 SRP72 Zornitza Stark reviewed gene: SRP72: Rating: AMBER; Mode of pathogenicity: None; Publications: 22541560, 31254415; Phenotypes: Bone marrow failure syndrome 1, MIM# 614675; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4435 SLC25A38 Zornitza Stark Mode of inheritance for gene: SLC25A38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4434 SLC25A38 Zornitza Stark reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: None; Publications: 19412178; Phenotypes: Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4432 SLC19A2 Zornitza Stark Mode of inheritance for gene: SLC19A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4431 SLC19A2 Zornitza Stark reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391221, 10978358; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4429 SEC23B Zornitza Stark Mode of inheritance for gene: SEC23B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4428 SEC23B Zornitza Stark reviewed gene: SEC23B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19561605, 19621418; Phenotypes: Dyserythropoietic anemia, congenital, type II , MIM#224100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4426 RPS27 Zornitza Stark Mode of inheritance for gene: RPS27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4424 RPS27 Zornitza Stark reviewed gene: RPS27: Rating: RED; Mode of pathogenicity: None; Publications: 25424902; Phenotypes: Diamond-Blackfan anemia 17, MIM# 617409; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4422 RPS17 Zornitza Stark Mode of inheritance for gene: RPS17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4421 RPS17 Zornitza Stark reviewed gene: RPS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 17647292, 19061985, 23812780, 23718193; Phenotypes: Diamond-Blackfan anemia 4, MIM# 612527; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4421 RPL9 Zornitza Stark gene: RPL9 was added
gene: RPL9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RPL9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL9 were set to 29114930; 20116044
Phenotypes for gene: RPL9 were set to Diamond Blackfan anaemia
Review for gene: RPL9 was set to RED
Added comment: PMID: 29114930, de novo splice site variant, c.-2+1G>C, functional impact of this variant is likely deleterious but not proven. Inherited missense variant reported in PMID 20116044, p.Arg125Ser is present in 31 hets in gnomad.
Sources: Expert list
Mendeliome v0.4418 RPL31 Zornitza Stark Mode of inheritance for gene: RPL31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4416 RPL31 Zornitza Stark reviewed gene: RPL31: Rating: AMBER; Mode of pathogenicity: None; Publications: 25042156, 25424902; Phenotypes: Diamond Blackfan anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4414 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4413 PUS1 Zornitza Stark reviewed gene: PUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25227147, 17056637, 15108122, 32287105, 31641589, 28832011; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4412 NHP2 Zornitza Stark Phenotypes for gene: NHP2 were changed from to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987
Mendeliome v0.4410 NHP2 Zornitza Stark Mode of inheritance for gene: NHP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4409 NHP2 Zornitza Stark reviewed gene: NHP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18523010, 31985013; Phenotypes: Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4409 GGT1 Elena Savva reviewed gene: GGT1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29483667, 23615310; Phenotypes: ?Glutathioninuria 231950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4407 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4406 LIG4 Zornitza Stark reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11779494, 16088910, 15333585, 20133615; Phenotypes: LIG4 syndrome, MIM# 606593; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4404 HOXA11 Zornitza Stark Mode of inheritance for gene: HOXA11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4402 HOXA11 Zornitza Stark reviewed gene: HOXA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 11101832, 16765069; Phenotypes: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, MIM# 605432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4400 TGM6 Zornitza Stark Mode of inheritance for gene: TGM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4398 TGM6 Zornitza Stark reviewed gene: TGM6: Rating: RED; Mode of pathogenicity: None; Publications: 30670339, 32426513; Phenotypes: Spinocerebellar ataxia 35, MIM# 613908; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4396 SQSTM1 Zornitza Stark Mode of inheritance for gene: SQSTM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4393 SLC25A46 Zornitza Stark Mode of inheritance for gene: SLC25A46 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4392 SLC25A46 Zornitza Stark changed review comment from: Age of onset is variable, but childhood onset described. Ataxia is a feature.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus.

At least 10 unrelated families reported, supportive functional data.
Mendeliome v0.4390 RORA Zornitza Stark Mode of inheritance for gene: RORA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4389 RORA Zornitza Stark reviewed gene: RORA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29656859; Phenotypes: Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4389 MAPK8IP3 Zornitza Stark edited their review of gene: MAPK8IP3: Added comment: 18 unrelated individuals reported with de novo variants and a neurodevelopmental disorder characterised by global developmental delay, variably impaired intellectual development, and poor or absent speech. Additional features may include hypotonia, spasticity, or ataxia. About half have abnormal findings on brain imaging, including cerebral or cerebellar atrophy, loss of white matter volume, thin corpus callosum, and perisylvian polymicrogyria. Seizures are not a prominent finding, and nonspecific dysmorphic facial features are described.; Changed publications: 30612693, 30945334
Mendeliome v0.4387 LARS2 Zornitza Stark Mode of inheritance for gene: LARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4386 LARS2 Zornitza Stark reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Perrault syndrome 4, Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021, Leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4384 LAMA1 Zornitza Stark Mode of inheritance for gene: LAMA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4381 KCNA2 Zornitza Stark Mode of inheritance for gene: KCNA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4380 KCNA2 Zornitza Stark commented on gene: KCNA2: Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations.
Mendeliome v0.4378 HARS2 Zornitza Stark Mode of inheritance for gene: HARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4377 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31827252; Phenotypes: Perrault syndrome 2, MIM# 614926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4377 ELOVL5 Zornitza Stark reviewed gene: ELOVL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25065913; Phenotypes: Spinocerebellar ataxia 38, MIM# 615957; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4375 EBF3 Zornitza Stark Mode of inheritance for gene: EBF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4374 EBF3 Zornitza Stark reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28017373, 28017372, 28017370, 32366537; Phenotypes: Hypotonia, ataxia, and delayed development syndrome, MIM# 617330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4372 DOCK3 Zornitza Stark Mode of inheritance for gene: DOCK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4371 DOCK3 Zornitza Stark reviewed gene: DOCK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28195318, 29130632, 30976111; Phenotypes: Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4369 ATP8A2 Zornitza Stark Mode of inheritance for gene: ATP8A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4366 CNGB3 Zornitza Stark Mode of inheritance for gene: CNGB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4365 CNGB3 Zornitza Stark reviewed gene: CNGB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17265047; Phenotypes: Achromatopsia 3, MIM# 262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4363 CNGA3 Zornitza Stark Mode of inheritance for gene: CNGA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4362 CNGA3 Zornitza Stark reviewed gene: CNGA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9662398, 11536077, 17265047; Phenotypes: Achromatopsia 2, MIM# 216900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4360 SPRED1 Zornitza Stark Mode of inheritance for gene: SPRED1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4359 SPRED1 Zornitza Stark reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17704776, 19366998, 21548021; Phenotypes: Legius syndrome, MIM# 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4356 SOS2 Zornitza Stark reviewed gene: SOS2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 25795793, 32788663; Phenotypes: Noonan syndrome 9, MIM# 616559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4355 SOS1 Zornitza Stark edited their review of gene: SOS1: Added comment: Over 50 individuals reported with SOS1 variants and a Noonan syndrome phenotype. Pulmonic stenosis tends to be more frequent compared to those with PTPN11 mutations, and atrial septal defect is relatively rare. Ectodermal features including keratosis pilaris and curly hair are significantly more prevalent compared with the general Noonan population. Height below the third percentile and learning disability are observed in fewer individuals compared with Noonan syndrome in general. In contrast, macrocephaly is overrepresented among those with SOS1 mutations.; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 17143285, 17143282, 28884940, 17586837; Changed phenotypes: Noonan syndrome 4, MIM# 610733; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4352 SHOC2 Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4351 SHOC2 Zornitza Stark reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19684605, 23918763, 20882035; Phenotypes: Noonan syndrome-like with loose anagen hair 1, MIM# 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4348 RIT1 Zornitza Stark Mode of inheritance for gene: RIT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4347 RIT1 Zornitza Stark reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 23791108, 25124994, 24939608, 27101134; Phenotypes: Noonan syndrome 8, MIM# 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4344 NRAS Zornitza Stark Mode of inheritance for gene: NRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4343 NRAS Zornitza Stark reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19966803, 26467218, 28594414; Phenotypes: Noonan syndrome 6, MIM# 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4340 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4339 MAP2K2 Zornitza Stark reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20358587, 16439621, 18042262; Phenotypes: Cardiofaciocutaneous syndrome 4, MIM# 615280; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4336 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4335 MAP2K1 Zornitza Stark reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16439621, 17551924, 18042262, 20301365; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4332 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4331 HRAS Zornitza Stark reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16329078, 16372351, 16443854; Phenotypes: Costello syndrome, MIM# 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4328 CBL Zornitza Stark Mode of inheritance for gene: CBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4327 CBL Zornitza Stark reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 25358541, 20619386, 20543203, 20694012; Phenotypes: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia, MIM# 613563; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4325 CSNK1D Zornitza Stark Mode of inheritance for gene: CSNK1D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4323 CSNK1D Zornitza Stark reviewed gene: CSNK1D: Rating: AMBER; Mode of pathogenicity: None; Publications: 15800623, 23636092; Phenotypes: Advanced sleep-phase syndrome, familial, 2, MIM# 615224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4321 CACNA1E Zornitza Stark Mode of inheritance for gene: CACNA1E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4318 ATAD1 Zornitza Stark Mode of inheritance for gene: ATAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4317 ATAD1 Zornitza Stark changed review comment from: Severe progressive neurological disorder, severe/profound intellectual disability is a feature; to: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures. Severe progressive neurological disorder, severe/profound intellectual disability is a feature.
Mendeliome v0.4315 ADAT1 Zornitza Stark gene: ADAT1 was added
gene: ADAT1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAT1 were set to 28180185; 29390050; 29659736
Phenotypes for gene: ADAT1 were set to Hyperekplexia 4, MIM#618011
Review for gene: ADAT1 was set to GREEN
Added comment: Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Three unrelated families reported. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures.
Sources: Expert list
Mendeliome v0.4314 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous to Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous
Mendeliome v0.4312 OCA2 Zornitza Stark Phenotypes for gene: OCA2 were changed from to [Skin/hair/eye pigmentation 1, blond/brown hair] 227220; [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220; Albinism, brown oculocutaneous 203200; Albinism, oculocutaneous, type II 203200; autosomal dominant Albinism, oculocutaneous
Mendeliome v0.4310 OCA2 Zornitza Stark Mode of inheritance for gene: OCA2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4309 OCA2 Elena Savva reviewed gene: OCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32741191, 24518832; Phenotypes: [Skin/hair/eye pigmentation 1, blond/brown hair] 227220, [Skin/hair/eye pigmentation 1, blue/nonblue eyes] 227220, Albinism, brown oculocutaneous 203200, Albinism, oculocutaneous, type II 203200, autosomal dominant Albinism, oculocutaneous; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.4309 ZSWIM6 Zornitza Stark changed review comment from: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X) identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp
Mendeliome v0.4309 ZSWIM6 Zornitza Stark changed review comment from: MIM #617865 A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671: recurrent missense identified in 6 unrelated families, p.Arg1163Trp; to: MIM #617865 (NEDMAGA): A recurrent de novo heterozygous truncating mutation in the ZSWIM6 gene (R913X)identified in 7 unrelated patients. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Possible dominant-negative effect. NB a more proximal nonsense variant was also reported inherited in a family with an unaffected mother: loss of function variants may not cause a phenotype.
MIM#603671 (acromelic frontonasal dysplasia): recurrent missense identified in 6 unrelated families, p.Arg1163Trp
Mendeliome v0.4308 SREBF1 Zornitza Stark reviewed gene: SREBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4308 VPS13D Zornitza Stark Phenotypes for gene: VPS13D were changed from to Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317
Mendeliome v0.4306 VPS13D Zornitza Stark Mode of inheritance for gene: VPS13D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4304 FARSA Zornitza Stark gene: FARSA was added
gene: FARSA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSA were set to 31355908
Phenotypes for gene: FARSA were set to Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Review for gene: FARSA was set to RED
Added comment: Autosomal recessive disorder characterized by growth delay, interstitial lung disease, liver disease, and abnormal brain MRI findings, including brain calcifications and periventricular cysts. Single affected individual reported, but FARSA interacts with FARSB, which causes a similar disorder.
Sources: Expert list
Mendeliome v0.4301 SLC1A3 Zornitza Stark Mode of inheritance for gene: SLC1A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4300 SLC1A3 Zornitza Stark reviewed gene: SLC1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19139306, 16116111, 29208948, 27829685; Phenotypes: Episodic ataxia, type 6, MIM# 612656; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4299 ANGPT2 Zornitza Stark gene: ANGPT2 was added
gene: ANGPT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANGPT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPT2 were set to https://stm.sciencemag.org/content/12/560/eaax8013
Phenotypes for gene: ANGPT2 were set to Primary lymphoedema
Review for gene: ANGPT2 was set to GREEN
Added comment: Five unrelated individuals reported with primary lymphedema and variants in this gene, together with functional data.
Sources: Literature
Mendeliome v0.4296 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4295 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4293 SLC16A2 Zornitza Stark Mode of inheritance for gene: SLC16A2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4292 SLC16A2 Zornitza Stark reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15980113, 31410843, 20301789; Phenotypes: Allan-Herndon-Dudley syndrome, MIM# 300523; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4290 TRIP13 Zornitza Stark Mode of inheritance for gene: TRIP13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4289 TRIP13 Zornitza Stark reviewed gene: TRIP13: Rating: GREEN; Mode of pathogenicity: None; Publications: 28553959, 32473092; Phenotypes: Mosaic variegated aneuploidy syndrome 3, MIM# 617598, Oocyte maturation defect 9, MIM# 619011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4286 NOBOX Zornitza Stark Mode of inheritance for gene: NOBOX was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4285 NOBOX Zornitza Stark reviewed gene: NOBOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 27836978, 21837770, 25514101, 17701902, 27798098, 29067606; Phenotypes: Premature ovarian failure 5,MIM#611548; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4284 TET2 Zornitza Stark Phenotypes for gene: TET2 were changed from Dementia; Lymphoma/myeloid malignancy to Dementia; Lymphoma/myeloid malignancy; Immunodeficiency
Mendeliome v0.4283 TET2 Zornitza Stark Mode of inheritance for gene: TET2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4279 TLR7 Zornitza Stark Mode of inheritance for gene: TLR7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4276 EXOSC5 Zornitza Stark Mode of inheritance for gene: EXOSC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4275 EXOSC5 Arina Puzriakova reviewed gene: EXOSC5: Rating: ; Mode of pathogenicity: None; Publications: 32504085, 29302074; Phenotypes: Short stature, Motor developmental delays, Cerebellar hypoplasia, Ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4273 SLC20A1 Zornitza Stark Mode of inheritance for gene: SLC20A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4272 SLC20A1 Zornitza Stark reviewed gene: SLC20A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32850778, 27013921; Phenotypes: Bladder-Exstrophy-Epispadias Complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4270 PNPLA8 Zornitza Stark Mode of inheritance for gene: PNPLA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4267 NR2F1 Zornitza Stark Mode of inheritance for gene: NR2F1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4266 NR2F1 Zornitza Stark reviewed gene: NR2F1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32275123; Phenotypes: Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4264 RAD50 Zornitza Stark Mode of inheritance for gene: RAD50 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4263 RAD50 Zornitza Stark reviewed gene: RAD50: Rating: GREEN; Mode of pathogenicity: None; Publications: 19409520, 32212377; Phenotypes: Nijmegen breakage syndrome-like disorder, MIM# 613078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4262 CFAP58 Zornitza Stark Phenotypes for gene: CFAP58 were changed from Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035) to Multiple morphological abnormalities of the sperm flagella (MMAF)
Mendeliome v0.4259 WASHC4 Zornitza Stark gene: WASHC4 was added
gene: WASHC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASHC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASHC4 were set to 31953988; 21498477
Phenotypes for gene: WASHC4 were set to Mental retardation, autosomal recessive 43, MIM #615817
Review for gene: WASHC4 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Mendeliome v0.4257 DNAJC7 Seb Lunke gene: DNAJC7 was added
gene: DNAJC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DNAJC7 were set to 31768050
Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis
Review for gene: DNAJC7 was set to AMBER
Added comment: Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. However gene described as risk factor, unclear why.

DOI: https://doi.org/10.1212/NXG.0000000000000503
Sources: Literature
Mendeliome v0.4256 CFAP58 Crystle Lee edited their review of gene: CFAP58: Added comment: Biallelic variants reported in 5 unrelated males with nultiple morphological abnormalities of the sperm flagella (MMAF). Knockout mice were infertile.; Changed rating: GREEN; Changed publications: 32791035; Changed phenotypes: Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035); Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4256 HSPA9 Zornitza Stark Phenotypes for gene: HSPA9 were changed from to Anemia, sideroblastic, 4, MIM# 182170; Even-plus syndrome, MIM#616854; skeletal anomalies; congenital cardiac and renal anomalies: marked small nose
Mendeliome v0.4254 HSPA9 Zornitza Stark Mode of inheritance for gene: HSPA9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4253 HSPA9 Seb Lunke Mode of inheritance for gene: HSPA9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4251 CFAP57 Zornitza Stark Mode of inheritance for gene: CFAP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 CFAP57 Zornitza Stark reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: 21574244, 32764743; Phenotypes: Van der Woude Syndrome, Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 HSPA9 Sue White reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26598328, 32869452; Phenotypes: https://www.omim.org/entry/616854, skeletal anomalies, congenital cardiac and renal anomalies: marked small nose; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 SVIL Melanie Marty gene: SVIL was added
gene: SVIL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SVIL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVIL were set to 32779703
Phenotypes for gene: SVIL were set to myopathy
Penetrance for gene: SVIL were set to unknown
Review for gene: SVIL was set to GREEN
Added comment: Four patients from two unrelated consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. Functional studies on muscle biopsies showed complete loss protein in muscle fibres by western blot.
Sources: Literature
Mendeliome v0.4250 HSPA9 Zornitza Stark reviewed gene: HSPA9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Anemia, sideroblastic, 4, MIM# 182170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4250 CFAP58 Crystle Lee gene: CFAP58 was added
gene: CFAP58 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CFAP58 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP58 were set to 32791035
Phenotypes for gene: CFAP58 were set to Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035)
Review for gene: CFAP58 was set to AMBER
Added comment: 5 unrelated males reported with biallelic loss of function variants. Knockout mice were infertile (Abstract only)
Sources: Expert Review
Mendeliome v0.4247 ARID1A Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4246 PDE10A Zornitza Stark Phenotypes for gene: PDE10A were changed from to Dyskinesia, limb and orofacial, infantile-onset, MIM#616921; Striatal degeneration, autosomal dominant, MIM# 616922
Mendeliome v0.4244 PDE10A Zornitza Stark Mode of inheritance for gene: PDE10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4243 PDE10A Zornitza Stark reviewed gene: PDE10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27058446, 27058447; Phenotypes: Dyskinesia, limb and orofacial, infantile-onset, MIM#616921, Striatal degeneration, autosomal dominant, MIM# 616922; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4242 MYSM1 Zornitza Stark changed review comment from: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay
Sources: Expert list; to: Early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay. At least 4 unrelated families reported.
Sources: Expert list
Mendeliome v0.4242 PNPLA8 Kristin Rigbye reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29681094, 25512002; Phenotypes: Mitochondrial myopathy with lactic acidosis (MIM#251950), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4242 ARID1A Crystle Lee reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23929686, 22426308, 25168959; Phenotypes: Coffin-Siris syndrome 2 (MIM#614607); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4241 KIF1C Zornitza Stark Phenotypes for gene: KIF1C were changed from to Spastic ataxia 2, autosomal recessive, MIM# 611302
Mendeliome v0.4239 KIF1C Zornitza Stark Mode of inheritance for gene: KIF1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4238 KIF1C Zornitza Stark reviewed gene: KIF1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24319291, 31413903, 29544888; Phenotypes: Spastic ataxia 2, autosomal recessive, MIM# 611302; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4236 GTPBP2 Zornitza Stark Mode of inheritance for gene: GTPBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4235 GTPBP2 Zornitza Stark reviewed gene: GTPBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26675814, 29449720, 30790272; Phenotypes: Jaberi-Elahi syndrome, MIM#617988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4235 GNB1 Zornitza Stark Phenotypes for gene: GNB1 were changed from to Mental retardation, autosomal dominant 42, MIM# 616973
Mendeliome v0.4233 GNB1 Zornitza Stark Mode of inheritance for gene: GNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4232 GNB1 Zornitza Stark reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27108799, 30194818, 27668284, 31034681; Phenotypes: Mental retardation, autosomal dominant 42, MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4231 SSBP1 Zornitza Stark Phenotypes for gene: SSBP1 were changed from Optic atrophy with or without extraocular phenotypes to Optic atrophy with or without extraocular phenotypes; Optic atrophy-13 with retinal and foveal abnormalities, MIM#165510
Mendeliome v0.4230 SSBP1 Zornitza Stark reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic atrophy-13 with retinal and foveal abnormalities, MIM#165510; Mode of inheritance: None
Mendeliome v0.4230 MCM10 Zornitza Stark gene: MCM10 was added
gene: MCM10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCM10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM10 were set to 32865517
Phenotypes for gene: MCM10 were set to Susceptibility to CMV
Review for gene: MCM10 was set to RED
Added comment: Compound heterozygous variants in minichromosomal maintenance complex member 10 (MCM10) reported as a cause of NK-cell deficiency in a child with fatal susceptibility to CMV.
Sources: Literature
Mendeliome v0.4229 TET2 Zornitza Stark changed review comment from: Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.; to: Mono-allelic variants: Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.
Mendeliome v0.4229 TET2 Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.; to: Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.
Mendeliome v0.4229 TET2 Zornitza Stark edited their review of gene: TET2: Added comment: PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.; Changed rating: GREEN; Changed publications: 30890702, 31827242, 32330418, 32518946; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4227 FDXR Zornitza Stark Mode of inheritance for gene: FDXR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4226 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Four families reported with bi-allelic variants in FDXR causing an autosomal recessive neurologic disorder characterised by onset of visual and hearing impairment in the first or second decades. Two individuals described with a more severe progressive neurological phenotype. Mouse model exhibits neurodegeneration.; Changed rating: GREEN; Changed publications: 30250212, 28965846
Mendeliome v0.4223 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4222 EIF2S3 Zornitza Stark reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140, 32799315; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4218 TRAPPC6B Zornitza Stark Mode of inheritance for gene: TRAPPC6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4217 TRAPPC6B Zornitza Stark reviewed gene: TRAPPC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28626029, 28397838, 31687267; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4215 TRAPPC12 Zornitza Stark Mode of inheritance for gene: TRAPPC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4214 TRAPPC12 Zornitza Stark reviewed gene: TRAPPC12: Rating: GREEN; Mode of pathogenicity: None; Publications: 32369837, 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4212 TPRKB Zornitza Stark Mode of inheritance for gene: TPRKB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4211 TPRKB Zornitza Stark reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, MIM# 617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4209 TP53RK Zornitza Stark Mode of inheritance for gene: TP53RK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4208 TP53RK Zornitza Stark reviewed gene: TP53RK: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 4, MIM# 617730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4206 TBC1D20 Zornitza Stark Mode of inheritance for gene: TBC1D20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4205 TBC1D20 Zornitza Stark reviewed gene: TBC1D20: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239381, 32740904, 32162791; Phenotypes: Warburg micro syndrome 4, MIM# 615663, Martsolf syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4205 DHX34 Zornitza Stark gene: DHX34 was added
gene: DHX34 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX34 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DHX34 were set to 31256877
Phenotypes for gene: DHX34 were set to Intellectual disability; congenital anomalies
Review for gene: DHX34 was set to RED
Added comment: Three families reported. Two with bi-allelic variants and ID/multiple congenital anomalies but another molecular diagnosis present in both (variants in established genes). Single de novo missense in another individual with ID and dysmorphism. No supporting functional data. Overall RED rating for both MOI.
Sources: Literature
Mendeliome v0.4204 DDX54 Zornitza Stark gene: DDX54 was added
gene: DDX54 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX54 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DDX54 were set to 31256877
Phenotypes for gene: DDX54 were set to Intellectual disability; congenital anomalies
Review for gene: DDX54 was set to RED
Added comment: Three individuals reported with different MOIs and different phenotypes. One with de novo variant and ID, another with bi-allelic variants and ID, and a third with bi-allelic variants and CAKUT. All variants are missense, no functional data. Overall, Red rating given inconsistent phenotypes and modes of inheritance, each one is essentially treated separately for now until further cases identified.
Sources: Literature
Mendeliome v0.4202 DHX16 Zornitza Stark gene: DHX16 was added
gene: DHX16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX16 were set to 31256877
Phenotypes for gene: DHX16 were set to Neuromuscular disease and ocular or auditory anomalies with or without seizures, MIM# 618733
Review for gene: DHX16 was set to GREEN
Added comment: Four unrelated individuals reported with de novo missense variants in this gene. Three of the individuals died in infancy, so phenotypic spectrum difficult to discern. Two had seizures. Individual with long-term survival had a progressive course, evidence of myopathy, loss of hearing and vision, and normal IQ.
Sources: Literature
Mendeliome v0.4201 DHX37 Zornitza Stark Phenotypes for gene: DHX37 were changed from 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS); Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731
Mendeliome v0.4199 DHX37 Zornitza Stark Mode of inheritance for gene: DHX37 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4198 DHX37 Zornitza Stark edited their review of gene: DHX37: Added comment: Bi-allelic disease: 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype, which also includes congenital anomalies particularly affecting the vertebrae and heart, but also some with microcephaly, brain anomalies.; Changed publications: 31337883, 31745530, 26539891, 31256877; Changed phenotypes: 46,XY gonadal dysgenesis, testicular regression syndrome (TRS), Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4198 CFL2 Zornitza Stark Phenotypes for gene: CFL2 were changed from to Nemaline myopathy 7, autosomal recessive, MIM# 610687
Mendeliome v0.4196 CFL2 Zornitza Stark Mode of inheritance for gene: CFL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4195 CFL2 Zornitza Stark reviewed gene: CFL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160903, 22560515, 32697999, 29457652, 24610938; Phenotypes: Nemaline myopathy 7, autosomal recessive, MIM# 610687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4193 TDRD7 Zornitza Stark reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cataract 36, MIM# 613887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4191 PAK3 Zornitza Stark Mode of inheritance for gene: PAK3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4190 PAK3 Zornitza Stark reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9731525, 10946356, 12884430, 17853471, 18523455, 32050918, 32005903, 31943058, 31843706, 31678216; Phenotypes: Mental retardation, X-linked 30/47, MIM# 300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4190 CFL2 Arina Puzriakova reviewed gene: CFL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32160286; Phenotypes: Nemaline myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4190 TDRD7 Arina Puzriakova reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32420594; Phenotypes: Congenital cataracts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4190 CLTC Zornitza Stark Phenotypes for gene: CLTC were changed from to Mental retardation, autosomal dominant 56, MIM# 617854
Mendeliome v0.4188 CLTC Zornitza Stark Mode of inheritance for gene: CLTC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4187 CLTC Zornitza Stark reviewed gene: CLTC: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083, 26822784; Phenotypes: Mental retardation, autosomal dominant 56, MIM# 617854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4187 PAK3 Arina Puzriakova reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31943058; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4187 SLC1A4 Zornitza Stark reviewed gene: SLC1A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25930971, 26138499, 26041762, 27193218, 29989513; Phenotypes: Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4185 RPL10 Zornitza Stark Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4184 RPL10 Zornitza Stark reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 25846674, 26290468; Phenotypes: Mental retardation, X-linked, syndromic, 35, MIM# 300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4184 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from to Cranioectodermal dysplasia 1, MIM# MIM#218330
Mendeliome v0.4182 IFT122 Zornitza Stark Mode of inheritance for gene: IFT122 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4181 IFT122 Zornitza Stark reviewed gene: IFT122: Rating: GREEN; Mode of pathogenicity: None; Publications: 26792575, 28370949, 29037998; Phenotypes: Cranioectodermal dysplasia 1, MIM# MIM#218330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4174 RARS2 Zornitza Stark Mode of inheritance for gene: RARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4173 RARS2 Zornitza Stark edited their review of gene: RARS2: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4173 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4170 RAB3GAP2 Zornitza Stark Mode of inheritance for gene: RAB3GAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4169 RAB3GAP2 Zornitza Stark reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23420520, 20967465; Phenotypes: Warburg micro syndrome 2, MIM# 614225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4167 RAB3GAP1 Zornitza Stark Mode of inheritance for gene: RAB3GAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4166 RAB3GAP1 Zornitza Stark reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15696165, 20512159, 23420520; Phenotypes: Warburg micro syndrome 1, MIM# 600118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4164 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4163 RAB18 Zornitza Stark reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: None; Publications: 11237903, 23420520; Phenotypes: Warburg micro syndrome 3, MIM# 614222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4163 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Mendeliome v0.4161 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4160 PTPN23 Zornitza Stark reviewed gene: PTPN23: Rating: GREEN; Mode of pathogenicity: None; Publications: 31395947, 29899372, 29090338, 27848944, 25558065; Phenotypes: Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4160 PRUNE1 Zornitza Stark Phenotypes for gene: PRUNE1 were changed from to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies , MIM#617481
Mendeliome v0.4158 PRUNE1 Zornitza Stark Mode of inheritance for gene: PRUNE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4157 PRUNE1 Zornitza Stark reviewed gene: PRUNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891, 28334956; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies , MIM#617481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4155 POGZ Zornitza Stark Mode of inheritance for gene: POGZ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4154 POGZ Zornitza Stark reviewed gene: POGZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 26942287, 26739615; Phenotypes: White-Sutton syndrome, MIM# 616364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4152 POC1A Zornitza Stark Mode of inheritance for gene: POC1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4151 POC1A Zornitza Stark reviewed gene: POC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22840364, 22840363, 26374189, 26162852, 26791357; Phenotypes: Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, MIM# 614813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4151 PLK4 Zornitza Stark Phenotypes for gene: PLK4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171
Mendeliome v0.4149 PLK4 Zornitza Stark Mode of inheritance for gene: PLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4148 PLK4 Zornitza Stark reviewed gene: PLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25344692, 25320347, 27650967; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4146 PIGH Zornitza Stark Mode of inheritance for gene: PIGH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4145 PIGH Zornitza Stark reviewed gene: PIGH: Rating: GREEN; Mode of pathogenicity: None; Publications: 29573052, 29603516; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 17, MIM# 618010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4145 PCYT2 Zornitza Stark Phenotypes for gene: PCYT2 were changed from to Spastic paraplegia 82, autosomal recessive 618770; global developmental delay; regression; spastic parapesis or tetraparesis; epilepsy; progressive cerebral and cerebellar atrophy
Mendeliome v0.4144 PCYT2 Zornitza Stark Mode of inheritance for gene: PCYT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4143 PCYT2 Zornitza Stark reviewed gene: PCYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31637422; Phenotypes: Spastic paraplegia 82, autosomal recessive 618770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4142 TIMM8A Zornitza Stark Mode of inheritance for gene: TIMM8A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4139 TIMM8A Zornitza Stark reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11803487, 11405816; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4138 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from to Mental retardation, autosomal dominant 33 (MIM#616311)
Mendeliome v0.4136 DPP6 Zornitza Stark Mode of inheritance for gene: DPP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4134 DPP6 Zornitza Stark reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23832105; Phenotypes: Mental retardation, autosomal dominant 33 (MIM#616311); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4134 TRAPPC2L Arina Puzriakova changed review comment from: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature; to: Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications. Rating Amber as additional cases required to delineate the genotype-phenotype relationship.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.

Sources: Literature
Mendeliome v0.4134 TRAPPC2L Arina Puzriakova gene: TRAPPC2L was added
gene: TRAPPC2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRAPPC2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC2L were set to 30120216; 32843486
Phenotypes for gene: TRAPPC2L were set to Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331
Review for gene: TRAPPC2L was set to AMBER
Added comment: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature
Mendeliome v0.4134 TIMM8A Arina Puzriakova reviewed gene: TIMM8A: Rating: ; Mode of pathogenicity: None; Publications: 32820032; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4134 TOGARAM1 Arina Puzriakova gene: TOGARAM1 was added
gene: TOGARAM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOGARAM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOGARAM1 were set to 32747439
Phenotypes for gene: TOGARAM1 were set to Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus
Added comment: PMID: 32747439 (2020) - Novel gene-disease association. In two sibling fetuses with a malformation disorder characterised by microcephaly, severe cleft lip and palate, microphthalmia, and brain anomalies, WES revealed compound heterozygous variants ([c.1102C>T, p.Arg368Trp] and [c.3619C>T, p.Arg1207*]) in the TOGARAM1 gene.

Functional analysis of the missense variant in a C. elegans model showed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. In vitro analysis revealed faster microtubule polymerisation compared to wild-type, suggesting aberrant tubulin binding.
Sources: Literature
Mendeliome v0.4134 DPP6 Ain Roesley reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23832105; Phenotypes: Mental retardation, autosomal dominant 33 (MIM#616311); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4132 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4131 PCGF2 Zornitza Stark reviewed gene: PCGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM# 618371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4129 TRIT1 Zornitza Stark Mode of inheritance for gene: TRIT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4128 TRIT1 Zornitza Stark reviewed gene: TRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32088416, 24901367, 28185376, 30977854; Phenotypes: Combined oxidative phosphorylation deficiency 35, MIM#617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4126 CREBBP Zornitza Stark Mode of inheritance for gene: CREBBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4125 CREBBP Zornitza Stark reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10699051, 17855048, 27311832, 29460469; Phenotypes: Rubinstein-Taybi syndrome 1, MIM# 180849, Menke-Hennekam syndrome 1, MIM# 618332; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4125 CRIPT Ain Roesley gene: CRIPT was added
gene: CRIPT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRIPT were set to 24389050; 27250922
Phenotypes for gene: CRIPT were set to Short stature with microcephaly and distinctive facies (MIM#615789)
Penetrance for gene: CRIPT were set to unknown
Review for gene: CRIPT was set to AMBER
Added comment: PMID: 24389050
- 2 unrelated probands homozygous for PTVs. However 1 was deceased and DNA was unavailable therefore parents were sequenced

PMID: 27250922
- 1x proband
- het for a missense which was maternally inherited. Because the father was negative for SNVs, they did CMA and found a small heterozygous deletion 1.6kb in size encompassing exon 1 of CRIPT. This deletion was paternally inherited

*did not find new reports since
Sources: Literature
Mendeliome v0.4125 FANCD2 Dean Phelan reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:20301575; Phenotypes: Fanconi anemia 227646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4123 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4121 UFC1 Paul De Fazio gene: UFC1 was added
gene: UFC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776; 30552426
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth (MIM#618076)
Review for gene: UFC1 was set to GREEN
gene: UFC1 was marked as current diagnostic
Added comment: PMID 29868776: 8 affected individuals from 4 families reported. 7 were described to be postnatally microcephalic (at or below 3rd percentile). One was -5.1SD and one was -3.6SD. SD values for the others weren't provided.

The following head circumference measurements were provided for 6 of the affecteds:

51cm at 16yo; 50cm at 19yo; 42.5cm at 12mo, 45cm at 28mo, 45.2cm at 7yo; 45cm at 4yo.

3 of the families were consanguineous Saudi families with the same homozygous missense variant.

In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1. Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and the authors suggested that complete loss of function would be embryonic lethal.

PMID 30552426: 1 more individual with epileptic encephalopathy reported with a different homozygous missense variant in UFC1. The patient had microcephaly <3rd percentile.
Sources: Literature
Mendeliome v0.4121 CENPE Seb Lunke Phenotypes for gene: CENPE were changed from to Microcephaly 13, primary, autosomal recessive (MIM#616051)
Mendeliome v0.4119 CENPE Seb Lunke Mode of inheritance for gene: CENPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4117 CENPE Ain Roesley reviewed gene: CENPE: Rating: RED; Mode of pathogenicity: None; Publications: 24748105, 30086807; Phenotypes: Microcephaly 13, primary, autosomal recessive (MIM#616051); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4115 CDC6 Seb Lunke Mode of inheritance for gene: CDC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4114 DIAPH1 Dean Phelan reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24781755, 26463574, 24781755, 27808407, 28003573, 28815995; Phenotypes: Deafness, thrombocytopenia, Seizures, cortical blindness, microcephaly; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4113 CDC6 Ain Roesley reviewed gene: CDC6: Rating: RED; Mode of pathogenicity: None; Publications: 21358632; Phenotypes: Meier-Gorlin syndrome 5 (MIM#613805); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4112 CTNND1 Zornitza Stark reviewed gene: CTNND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28301459; Phenotypes: Blepharocheilodontic syndrome 2, MIM# 617681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4111 CTNND1 Zornitza Stark Mode of inheritance for gene: CTNND1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4109 RIPOR2 Zornitza Stark Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal recessive 104, MIM# 616515 to Deafness, autosomal recessive 104, MIM# 616515; Deafness, autosomal dominant
Mendeliome v0.4108 RIPOR2 Zornitza Stark changed review comment from: Single family and animal model data.
Sources: Expert list; to: Single family with bi-allelic variants and animal model data.
Sources: Expert list
Mendeliome v0.4107 RIPOR2 Zornitza Stark Mode of inheritance for gene: RIPOR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4105 TET2 Zornitza Stark Phenotypes for gene: TET2 were changed from to Dementia; Lymphoma/myeloid malignancy
Mendeliome v0.4104 TET2 Zornitza Stark Mode of inheritance for gene: TET2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4102 TET2 Zornitza Stark edited their review of gene: TET2: Changed phenotypes: Dementia, Lymphoma/myeloid malignancy; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4099 TRPM7 Zornitza Stark Mode of inheritance for gene: TRPM7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4097 TRPM7 Zornitza Stark edited their review of gene: TRPM7: Added comment: Ion channel expressed in the nervous and cardiac systems. The variant associated with ALS/dementia in the Guam population, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association.; Changed rating: AMBER; Changed publications: 32503408, 31423533; Changed phenotypes: {Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}, MIM# 105500, Cardiac arrhythmia, stillbirth; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4097 CHCHD10 Zornitza Stark Phenotypes for gene: CHCHD10 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911; Spinal muscular atrophy, Jokela type 615048; Myopathy, isolated mitochondrial, autosomal dominant 616209
Mendeliome v0.4094 CHCHD10 Zornitza Stark Mode of inheritance for gene: CHCHD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4093 CHCHD10 Zornitza Stark reviewed gene: CHCHD10: Rating: GREEN; Mode of pathogenicity: Other; Publications: 24934289, 25428574, 25193783, 32042922, 31690696, 30877432, 30874923; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 615911, Spinal muscular atrophy, Jokela type 615048, Myopathy, isolated mitochondrial, autosomal dominant 616209; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4091 CTNND1 Eleanor Williams changed review comment from: PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13).; to: PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13).
Mendeliome v0.4091 RIPOR2 Arina Puzriakova reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32631815; Phenotypes: Sensorineural hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.4091 NOTCH3 Eleanor Williams gene: NOTCH3 was added
gene: NOTCH3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NOTCH3 were set to 31960911
Phenotypes for gene: NOTCH3 were set to CADASIL
Review for gene: NOTCH3 was set to AMBER
Added comment: PMID: 31960911 - Gravesteijn et al 2020 - describe a family with a unique cysteine-altering NOTCH3 variant in exon 9 in 5 individuals, which is predicted to cause natural exon 9 skipping. This mimics the therapeutic NOTCH3 cysteine correction approach and allows the effect of cysteine corrective exon skipping on NOTCH3 protein aggregation and disease severity in humans to be studied. In this family the CADASIL phenotype was mild.

Note this gene is rated green on the Neurodegenerative disorders - adult onset panel in the Genomics England instance of PanelApp https://panelapp.genomicsengland.co.uk/panels/474/gene/NOTCH3/
Sources: Literature
Mendeliome v0.4091 ZFYVE19 Arina Puzriakova gene: ZFYVE19 was added
gene: ZFYVE19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFYVE19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE19 were set to 32737136
Phenotypes for gene: ZFYVE19 were set to Cholestasis
Review for gene: ZFYVE19 was set to GREEN
Added comment: PMID: 32737136 (2020) - Nine Han Chinese children from seven families with biallelic, predicted complete LoF variants in ZFYVE19. All patients had high-GGT intrahepatic cholestasis, portal hypertension, and histopathological features of the ductal plate malformation/congenital hepatic fibrosis.

ZFYVE19 depletion in cultured cells from one patient yielded centriolar and axonemal abnormalities, and immunostaining for two ciliary proteins DCDC2 and ACALT showed abnormal localisation in patient cholangiocytes, indicating this as a novel ciliopathy disorder.
Sources: Literature
Mendeliome v0.4091 TRPM7 Eleanor Williams reviewed gene: TRPM7: Rating: AMBER; Mode of pathogenicity: None; Publications: 31423533, 29874177; Phenotypes: still birth, cardiac development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4091 ADARB1 Arina Puzriakova reviewed gene: ADARB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220291, 32719099; Phenotypes: Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4089 SRD5A3 Zornitza Stark Mode of inheritance for gene: SRD5A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4088 KIF14 Zornitza Stark Phenotypes for gene: KIF14 were changed from to Microcephaly 20, primary, autosomal recessive, MIM# 617914; Meckel syndrome 12, MIM# 616258
Mendeliome v0.4086 KIF14 Zornitza Stark Mode of inheritance for gene: KIF14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4085 KIF14 Zornitza Stark reviewed gene: KIF14: Rating: GREEN; Mode of pathogenicity: None; Publications: 28892560, 29343805, 24128419; Phenotypes: Microcephaly 20, primary, autosomal recessive, MIM# 617914, Meckel syndrome 12, MIM# 616258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4083 KIF1BP Zornitza Stark Mode of inheritance for gene: KIF1BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4082 KIF1BP Zornitza Stark reviewed gene: KIF1BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23427148; Phenotypes: Goldberg-Shprintzen megacolon syndrome, MIM# 609460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4080 TRIP11 Zornitza Stark Mode of inheritance for gene: TRIP11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4077 PRF1 Zornitza Stark Mode of inheritance for gene: PRF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4074 HLCS Zornitza Stark Mode of inheritance for gene: HLCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4073 HLCS Zornitza Stark reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holocarboxylase synthetase deficiency, MIM# 253270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4073 CA5A Zornitza Stark reviewed gene: CA5A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperammonemia due to carbonic anhydrase VA deficiency, 615751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4071 CA5A Zornitza Stark Mode of inheritance for gene: CA5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4068 MOCS1 Zornitza Stark reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9921896, 12754701; Phenotypes: Molybdenum cofactor deficiency A, MIM# 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4068 MOCS1 Zornitza Stark Mode of inheritance for gene: MOCS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4066 KDM1A Zornitza Stark reviewed gene: KDM1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26656649, 24838796, 27094131; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features 616728; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4065 KDM1A Zornitza Stark Mode of inheritance for gene: KDM1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4063 TRIP11 Elena Savva reviewed gene: TRIP11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31903676, 30728324; Phenotypes: Osteochondrodysplasia, 184260, Achondrogenesis, type IA, 200600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4061 PRF1 Elena Savva reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19487666; Phenotypes: Aplastic anemia 609135, Hemophagocytic lymphohistiocytosis, familial, 2 603553, Lymphoma, non-Hodgkin 605027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4060 COL11A1 Zornitza Stark Mode of inheritance for gene: COL11A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4059 HLCS Elena Savva reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10190325; Phenotypes: Holocarboxylase synthetase deficiency, 253270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4059 CA5A Elena Savva reviewed gene: CA5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26913920, 32381389; Phenotypes: Hyperammonemia due to carbonic anhydrase VA deficiency, 615751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4059 MOCS1 Elena Savva reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21031595; Phenotypes: Molybdenum cofactor deficiency A 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4059 KDM1A Elena Savva reviewed gene: KDM1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29559475, 27094131; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features 616728, Multiple myeloma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4059 COL11A1 Elena Savva reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 25073711, 30245514, 32427345, 27081569, 21035103; Phenotypes: Fibrochondrogenesis 1 (MIM#228520), Marshall syndrome (MIM#154780), Stickler syndrome, type II (MIM#604841), {Lumbar disc herniation, susceptibility to}, (MIM#603932), ?Deafness, autosomal dominant 37, (MIM#618533); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.4058 YRDC Zornitza Stark gene: YRDC was added
gene: YRDC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YRDC were set to 31481669
Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome
Review for gene: YRDC was set to GREEN
Added comment: Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data.
Sources: Literature
Mendeliome v0.4056 GON7 Zornitza Stark gene: GON7 was added
gene: GON7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON7 were set to 31481669
Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome
Review for gene: GON7 was set to GREEN
Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect. Clinical features included proteinuria, microcephaly, brain malformations and developmental delay. Supportive functional data.
Sources: Literature
Mendeliome v0.4053 LAGE3 Zornitza Stark Mode of inheritance for gene: LAGE3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4052 LAGE3 Zornitza Stark reviewed gene: LAGE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828; Phenotypes: Galloway-Mowat syndrome 2, X-linked, MIM# 301006; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.4052 LINGO1 Zornitza Stark Phenotypes for gene: LINGO1 were changed from to Mental retardation, autosomal recessive 64, MIM# 618103
Mendeliome v0.4050 LINGO1 Zornitza Stark Mode of inheritance for gene: LINGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4048 LINGO1 Zornitza Stark reviewed gene: LINGO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31668702; Phenotypes: Mental retardation, autosomal recessive 64, MIM# 618103; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4046 OSGEP Zornitza Stark Mode of inheritance for gene: OSGEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4045 OSGEP Zornitza Stark reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 28272532; Phenotypes: Galloway-Mowat syndrome 3, MIM# 617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4043 NUP107 Zornitza Stark Mode of inheritance for gene: NUP107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4042 NUP107 Zornitza Stark reviewed gene: NUP107: Rating: GREEN; Mode of pathogenicity: None; Publications: 28280135, 28117080, 30179222, 25558065; Phenotypes: Galloway-Mowat syndrome 7, MIM# 618348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4040 NSD2 Zornitza Stark Mode of inheritance for gene: NSD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4039 NSD2 Zornitza Stark reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345613, 31171569; Phenotypes: Microcephaly, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4039 NCAPH Zornitza Stark Phenotypes for gene: NCAPH were changed from to Microcephaly 23, primary, autosomal recessive 617985
Mendeliome v0.4037 NCAPH Zornitza Stark Mode of inheritance for gene: NCAPH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4035 NCAPH Zornitza Stark reviewed gene: NCAPH: Rating: RED; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 23, primary, autosomal recessive 617985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4034 ATRIP Ain Roesley gene: ATRIP was added
gene: ATRIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATRIP were set to 23144622
Phenotypes for gene: ATRIP were set to Seckel Syndrome
Penetrance for gene: ATRIP were set to unknown
Review for gene: ATRIP was set to RED
Added comment: PMID: 23144622;
- 1x proband from a consanguineous family
- progressive severe microcephaly (-9 to -10SD)
- cHet for a nonsense and a splice
Sources: Literature
Mendeliome v0.4034 AP4E1 Zornitza Stark Phenotypes for gene: AP4E1 were changed from to Spastic paraplegia 51, autosomal recessive, MIM# 613744
Mendeliome v0.4032 AP4E1 Zornitza Stark Mode of inheritance for gene: AP4E1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4031 AP4E1 Zornitza Stark reviewed gene: AP4E1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20972249, 21620353, 21937992; Phenotypes: Spastic paraplegia 51, autosomal recessive, MIM# 613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4031 AP4B1 Zornitza Stark Phenotypes for gene: AP4B1 were changed from to Spastic paraplegia 47, autosomal recessive, MIM# 614066
Mendeliome v0.4029 AP4B1 Zornitza Stark Mode of inheritance for gene: AP4B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4028 AP4B1 Zornitza Stark reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21620353, 22290197, 24700674, 24781758; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4028 ANKLE2 Zornitza Stark reviewed gene: ANKLE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25259927, 30214071, 31735666; Phenotypes: Microcephaly 16, primary, autosomal recessive, MIM# 616681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4026 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4025 ZSWIM6 Zornitza Stark Phenotypes for gene: ZSWIM6 were changed from to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, MIM# 617865; Acromelic frontonasal dysostosis, MIM# 603671
Mendeliome v0.4023 ZSWIM6 Zornitza Stark Mode of inheritance for gene: ZSWIM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4022 ZSWIM6 Zornitza Stark reviewed gene: ZSWIM6: Rating: GREEN; Mode of pathogenicity: None; Publications: 29198722, 25105228, 26706854; Phenotypes: Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, MIM# 617865, Acromelic frontonasal dysostosis, MIM# 603671; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4020 ABCB11 Zornitza Stark Mode of inheritance for gene: ABCB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4019 ABCB11 Zornitza Stark reviewed gene: ABCB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 16871584, 23141890, 9806540, 15300568, 11172067; Phenotypes: Cholestasis, progressive familial intrahepatic 2, MIM# 601847, Cholestasis, benign recurrent intrahepatic, 2, MIM# 605479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4017 ABCB1 Zornitza Stark Mode of inheritance for gene: ABCB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4015 ABCB1 Zornitza Stark reviewed gene: ABCB1: Rating: RED; Mode of pathogenicity: None; Publications: 14610718; Phenotypes: {Inflammatory bowel disease 13} 612244; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4013 ABCA3 Zornitza Stark Mode of inheritance for gene: ABCA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4012 ABCA3 Zornitza Stark reviewed gene: ABCA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15044640; Phenotypes: Surfactant metabolism dysfunction, pulmonary, 3, MIM# 610921; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4012 ABCA12 Zornitza Stark Phenotypes for gene: ABCA12 were changed from to Ichthyosis, congenital, autosomal recessive 4A (MIM#601277); Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500)
Mendeliome v0.4010 ABCA12 Zornitza Stark Mode of inheritance for gene: ABCA12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4009 ABCA12 Zornitza Stark reviewed gene: ABCA12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31168818, 19664001, 31489029; Phenotypes: Ichthyosis, congenital, autosomal recessive 4A (MIM#601277), Ichthyosis, congenital, autosomal recessive 4B (harlequin) (MIM#242500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4007 ABCA1 Zornitza Stark Mode of inheritance for gene: ABCA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4006 ABCA1 Zornitza Stark reviewed gene: ABCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431237, 10431236; Phenotypes: Tangier disease, MIM# 205400, HDL deficiency, familial, 1, MIM# 604091; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4004 AASS Zornitza Stark Mode of inheritance for gene: AASS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4002 AASS Zornitza Stark changed review comment from: Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic. Given the broad range of clinical features and the presence of consanguinity in several families, there was not strong evidence for causality of symptoms. Hyperlysinemia is generally considered to be a benign metabolic variant rather than a disease entity.; to: Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic. Given the broad range of clinical features and the presence of consanguinity in several families, there was not strong evidence for causality of symptoms. It has been suggested that hyperlysinemia is a benign metabolic variant rather than a disease entity.
Mendeliome v0.4002 AASS Zornitza Stark reviewed gene: AASS: Rating: RED; Mode of pathogenicity: None; Publications: 23570448; Phenotypes: Hyperlysinemia, MIM# 238700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4000 AARS2 Zornitza Stark Mode of inheritance for gene: AARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3999 AARS2 Zornitza Stark reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30706699, 27839525, 21549344, 25058219, 24808023; Phenotypes: Combined oxidative phosphorylation deficiency 8 MIM#614096, Leukoencephalopathy, progressive, with ovarian failure MIM#615889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3997 AARS Zornitza Stark Mode of inheritance for gene: AARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3996 AARS Zornitza Stark reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28493438, 25817015, 20045102, 22009580, 22206013, 30373780, 26032230; Phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3994 AAGAB Zornitza Stark Mode of inheritance for gene: AAGAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3993 AAGAB Zornitza Stark reviewed gene: AAGAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30451279, 26608363; Phenotypes: Keratoderma, palmoplantar, punctate type IA (MIM#148600); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3989 PAFAH1B1 Zornitza Stark Mode of inheritance for gene: PAFAH1B1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3988 PAFAH1B1 Zornitza Stark reviewed gene: PAFAH1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11754098, 18285425; Phenotypes: Lissencephaly 1, MIM# 607432, Subcortical laminar heterotopia, MIM# 607432, MONDO:0011830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3986 LAMB1 Zornitza Stark Mode of inheritance for gene: LAMB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3985 LAMB1 Zornitza Stark reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23472759, 25925986, 29888467, 25925986, 32548278; Phenotypes: Lissencephaly 5, MIM# 615191, Cystic leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3985 TMEM5 Zornitza Stark Phenotypes for gene: TMEM5 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041
Mendeliome v0.3983 TMEM5 Zornitza Stark Mode of inheritance for gene: TMEM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3982 TMEM5 Zornitza Stark reviewed gene: TMEM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23217329, 23519211; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3982 KIF5C Zornitza Stark Phenotypes for gene: KIF5C were changed from to Cortical dysplasia, complex, with other brain malformations 2, MIM# 615282
Mendeliome v0.3980 KIF5C Zornitza Stark Mode of inheritance for gene: KIF5C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3979 KIF5C Zornitza Stark reviewed gene: KIF5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 23603762, 23033978, 32562872; Phenotypes: Cortical dysplasia, complex, with other brain malformations 2, MIM# 615282; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3979 KIF2A Zornitza Stark Phenotypes for gene: KIF2A were changed from to Cortical dysplasia, complex, with other brain malformations 3, MIM# 615411
Mendeliome v0.3977 KIF2A Zornitza Stark Mode of inheritance for gene: KIF2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3976 KIF2A Zornitza Stark reviewed gene: KIF2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23603762, 27896282, 27747449, 29077851, 31919497; Phenotypes: Cortical dysplasia, complex, with other brain malformations 3, MIM# 615411; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3976 ISPD Zornitza Stark Phenotypes for gene: ISPD were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052
Mendeliome v0.3974 ISPD Zornitza Stark Mode of inheritance for gene: ISPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3973 ISPD Zornitza Stark reviewed gene: ISPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522421, 23217329, 23390185, 30060766, 28688748, 26404900; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7, MIM# 616052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3971 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3970 DCX Zornitza Stark reviewed gene: DCX: Rating: GREEN; Mode of pathogenicity: None; Publications: 10915612, 9489699, 12552055; Phenotypes: Lissencephaly, X-linked, MIM# 300067, Subcortical laminal heterotopia, X-linked 300067; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3970 TLR7 Zornitza Stark reviewed gene: TLR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32706371; Phenotypes: Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3970 ASPRV1 Zornitza Stark Phenotypes for gene: ASPRV1 were changed from palmoplantar keratoderma; lamellar ichthyosis to Ichthyosis, lamellar, autosomal dominant, MIM# 146750; palmoplantar keratoderma; lamellar ichthyosis
Mendeliome v0.3969 ASPRV1 Zornitza Stark reviewed gene: ASPRV1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, lamellar, autosomal dominant, MIM# 146750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3967 MRPL44 Zornitza Stark Mode of inheritance for gene: MRPL44 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3966 MRPL44 Zornitza Stark reviewed gene: MRPL44: Rating: GREEN; Mode of pathogenicity: None; Publications: 23315540, 25797485; Phenotypes: Combined oxidative phosphorylation deficiency 16, MIM# 615395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3966 KBTBD13 Zornitza Stark Phenotypes for gene: KBTBD13 were changed from to Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy; late-onset limb girdle muscular dystrophy
Mendeliome v0.3964 KBTBD13 Zornitza Stark Mode of inheritance for gene: KBTBD13 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3963 KBTBD13 Zornitza Stark reviewed gene: KBTBD13: Rating: ; Mode of pathogenicity: None; Publications: 11731279, 21104864; Phenotypes: Nemaline myopathy 6, autosomal dominant, MIM# 609273, Hereditary motor neuropathy, late-onset limb girdle muscular dystrophy; Mode of inheritance: None
Mendeliome v0.3961 KBTBD13 Elena Savva reviewed gene: KBTBD13: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28403181, 31167812, 31671076, 30208948; Phenotypes: Nemaline myopathy 6, autosomal dominant, 609273, Hereditary motor neuropathy, late-onset limb girdle muscular dystrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3961 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138
Mendeliome v0.3959 LAMA2 Zornitza Stark Mode of inheritance for gene: LAMA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3958 LAMA2 Zornitza Stark reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055037; Phenotypes: Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855, Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM# 618138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3958 GRIN2B Zornitza Stark Phenotypes for gene: GRIN2B were changed from to Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139
Mendeliome v0.3956 GRIN2B Zornitza Stark Mode of inheritance for gene: GRIN2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3955 GRIN2B Zornitza Stark reviewed gene: GRIN2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28377535; Phenotypes: Mental retardation, autosomal dominant 6, MIM# 613970, Epileptic encephalopathy, early infantile, 27, MIM# 616139; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3955 GRIN1 Zornitza Stark Phenotypes for gene: GRIN1 were changed from to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Mendeliome v0.3953 GRIN1 Zornitza Stark Mode of inheritance for gene: GRIN1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3952 GRIN1 Zornitza Stark reviewed gene: GRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29365063, 27164704, 27164704, 28051072; Phenotypes: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254, Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3948 SEC61A1 Zornitza Stark Mode of inheritance for gene: SEC61A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3947 SEC61A1 Zornitza Stark reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27392076, 32325141, 28782633; Phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, MIM# 617056, Hypogammaglobulinaemia, Neutropaenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3946 ALG12 Zornitza Stark Mode of inheritance for gene: ALG12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3945 ALG12 Zornitza Stark reviewed gene: ALG12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31481313; Phenotypes: Congenital disorder of glycosylation, type Ig, MIM# 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3943 ALG11 Zornitza Stark Mode of inheritance for gene: ALG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3942 ALG11 Zornitza Stark reviewed gene: ALG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30676690; Phenotypes: Congenital disorder of glycosylation, type Ip, MIM# 613661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3940 NPRL2 Zornitza Stark Mode of inheritance for gene: NPRL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3939 NPRL2 Dean Phelan reviewed gene: NPRL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26505888, 27173016, 28199897, 31594065; Phenotypes: focal seizures, frontal lobe epilepsy, nocturnal frontal lobe epilepsy, temporal lobe epilepsy, focal cortical dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3938 PDE2A Zornitza Stark gene: PDE2A was added
gene: PDE2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDE2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE2A were set to 32467598; 32196122; 29392776
Phenotypes for gene: PDE2A were set to Paroxysmal dyskinesia
Review for gene: PDE2A was set to GREEN
Added comment: Four unrelated families reported with childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy. One of the reports characterises the disorder as 'Rett-like'.
Sources: Literature
Mendeliome v0.3935 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3934 OTULIN Zornitza Stark reviewed gene: OTULIN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27523608, 27559085; Phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3932 RRAGC Zornitza Stark Mode of inheritance for gene: RRAGC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3930 RRAGC Zornitza Stark reviewed gene: RRAGC: Rating: RED; Mode of pathogenicity: None; Publications: 27234373; Phenotypes: Dilated cardiomyopathy, cataract; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3928 CRADD Zornitza Stark Phenotypes for gene: CRADD were changed from to Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Mendeliome v0.3926 CRADD Zornitza Stark Mode of inheritance for gene: CRADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3925 CRADD Zornitza Stark reviewed gene: CRADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 27773430; Phenotypes: Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3925 TDGF1 Zornitza Stark Phenotypes for gene: TDGF1 were changed from to Forebrain abnormalities
Mendeliome v0.3923 TDGF1 Zornitza Stark Mode of inheritance for gene: TDGF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3921 TDGF1 Zornitza Stark reviewed gene: TDGF1: Rating: RED; Mode of pathogenicity: None; Publications: 12073012; Phenotypes: Forebrain abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3921 GABRA6 Zornitza Stark gene: GABRA6 was added
gene: GABRA6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA6 were set to 21930603; 29215089; 19429026
Phenotypes for gene: GABRA6 were set to Benign familial inherited epilepsy; Childhood absence epilepsy
Review for gene: GABRA6 was set to RED
Added comment: One report in a cohort of patients with BFIE. Potential susceptibility allele in CAE.
Sources: Literature
Mendeliome v0.3918 TMTC3 Zornitza Stark Mode of inheritance for gene: TMTC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3917 TMTC3 Zornitza Stark reviewed gene: TMTC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27773428, 28973161; Phenotypes: Lissencephaly 8 (MIM#617255); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3915 ARFGEF2 Zornitza Stark Mode of inheritance for gene: ARFGEF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3914 ARFGEF2 Zornitza Stark reviewed gene: ARFGEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25160555, 26126837, 23812912; Phenotypes: Periventricular heterotopia with microcephaly (MIM#608097); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3912 SLC6A3 Zornitza Stark Mode of inheritance for gene: SLC6A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3911 SLC6A3 Zornitza Stark reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21112253; Phenotypes: Parkinsonism-dystonia, infantile, 1, MIM# 613135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3909 MAOA Zornitza Stark Mode of inheritance for gene: MAOA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3908 MAOA Zornitza Stark reviewed gene: MAOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25807999, 24169519; Phenotypes: Brunner syndrome, MIM# 300615; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3906 GPHN Zornitza Stark Mode of inheritance for gene: GPHN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3905 GPHN Zornitza Stark reviewed gene: GPHN: Rating: GREEN; Mode of pathogenicity: None; Publications: 22040219, 11095995, 26613940, 24561070, 23393157; Phenotypes: Molybdenum cofactor deficiency C, MIM# 615501, Epilepsy, Autism, Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3903 GLRB Zornitza Stark Mode of inheritance for gene: GLRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3902 GLRB Zornitza Stark reviewed gene: GLRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 21391991, 11929858, 27843043; Phenotypes: Hyperekplexia 2, MIM# 614619; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3902 GLRA1 Zornitza Stark Mode of inheritance for gene: GLRA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3901 GLRA1 Zornitza Stark edited their review of gene: GLRA1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3899 GLRA1 Zornitza Stark Mode of inheritance for gene: GLRA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3898 GLRA1 Zornitza Stark reviewed gene: GLRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8298642, 16832093; Phenotypes: Hyperekplexia 1, MIM# 149400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3896 GABRG2 Zornitza Stark Mode of inheritance for gene: GABRG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3895 GABRG2 Zornitza Stark reviewed gene: GABRG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11326274, 11326275, 27864268; Phenotypes: Epileptic encephalopathy, early infantile, 74 618396, Epilepsy, generalized, with febrile seizures plus, type 3 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3893 GABRB3 Zornitza Stark Mode of inheritance for gene: GABRB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3892 GABRB3 Zornitza Stark reviewed gene: GABRB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23934111, 27476654; Phenotypes: Epileptic encephalopathy, early infantile, 43, MIM# 617113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3890 FOLR1 Zornitza Stark Mode of inheritance for gene: FOLR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3889 FOLR1 Zornitza Stark reviewed gene: FOLR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732866, 30420205, 27743887; Phenotypes: Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3887 DBH Zornitza Stark Mode of inheritance for gene: DBH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3886 DBH Zornitza Stark reviewed gene: DBH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11857564; Phenotypes: Dopamine beta-hydroxylase deficiency, MIM#223360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3884 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3883 ARHGEF9 Zornitza Stark reviewed gene: ARHGEF9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31942680, 30048823, 29130122, 28620718; Phenotypes: Epileptic encephalopathy, early infantile, 8, MIM# 300607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3880 STAT5B Zornitza Stark Mode of inheritance for gene: STAT5B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3879 STAT5B Zornitza Stark reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29844444; Phenotypes: Growth hormone insensitivity with immunodeficiency, MIM# 245590; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3877 ALDH5A1 Zornitza Stark Mode of inheritance for gene: ALDH5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3876 ALDH5A1 Zornitza Stark reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9683595, 14635103, 32402538; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3874 ABAT Zornitza Stark Mode of inheritance for gene: ABAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3872 LMBRD2 Zornitza Stark gene: LMBRD2 was added
gene: LMBRD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LMBRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMBRD2 were set to 32820033; https://doi.org/10.1101/797787
Phenotypes for gene: LMBRD2 were set to Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye
Mode of pathogenicity for gene: LMBRD2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: LMBRD2 was set to GREEN
Added comment: 13 individuals with dn missense SNVs overall, overlapping features for 10 with available phenotype / a recurring variant has been identified in 2 different studies.

► Malhotra et al (2020 - PMID: 32820033) report on 10 unrelated individuals with de novo missense LMBRD2 variants. Features included DD (9/10), ID (6/8 of relevant age), microcephaly (7/10), seizures (5/10 - >=3 different variants), structural brain abnormalities (e.g. thin CC in 6/9), highly variable ocular abnormalities (5/10) and dysmorphic features in some (7/10 - nonspecific). All had variable prior non-diagnostic genetic tests (CMA, gene panel, mendeliome, karyotype). WES/WGS revealed LMBRD2 missense variants, in all cases de novo. A single individual had additional variants with weaker evidence of pathogenicity. 5 unique missense SNVs and 2 recurrent ones (NM_001007527:c.367T>C - p.Trp123Arg / c.1448G>A - p.Arg483His) were identified. These occurred in different exons. Variants were not present in gnomAD and all had several in silico predictions in favor of a deleterious effect. There was phenotypic variability among individuals with the same variant (e.g. seizures in 1/3 and microchephaly in 2/3 of those harboring R483H). The gene has a pLI of 0 (although o/e ranges from 0.23 to 0.55), %HI of 15.13 and z-score of 2.27. The authors presume that haploinsufficiency may not apply, and consider a gain-of-function/dominant-negative effect more likely. As the authors comment LMBRD2 (LMBR1 domain containing 2) encodes a membrane bound protein with poorly described function. It is widely expressed across tissues with notable expression in human brain (also in Drosophila, or Xenopus laevis). It displays high interspecies conservation. It has been suggested (Paek et al - PMID: 28388415) that LMBRD2 is a potential regulator of β2 adrenoreceptor signalling through involvement in GPCR signalling.

► Kaplanis et al (2020 - https://doi.org/10.1101/797787) in a dataset of 31058 parent-offspring trios (WES) previously identified 3 individuals with developmental disorder, harboring c.1448G>A - p.Arg483His. These individuals (1 from the DDD study, and 2 GeneDx patients) appear in Decipher. [ https://decipher.sanger.ac.uk/ddd/research-variant/40e17c78cc9655a6721006fc1e0c98db/overview ]. The preprint by Kaplanis et al is cited by Malhotra et al, with Arg483His reported in 6 patients overall in both studies.
Sources: Literature
Mendeliome v0.3871 KAT5 Zornitza Stark Phenotypes for gene: KAT5 were changed from to Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face
Mendeliome v0.3868 KAT5 Zornitza Stark Mode of inheritance for gene: KAT5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3866 KAT5 Konstantinos Varvagiannis reviewed gene: KAT5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32822602; Phenotypes: Severe global developmental delay, Intellectual disability, Seizures, Microcephaly, Behavioral abnormality, Sleep disturbance, Morphological abnormality of the central nervous system, Short stature, Oral cleft, Abnormality of the face; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3866 AFG3L2 Zornitza Stark Phenotypes for gene: AFG3L2 were changed from to Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246); Optic atrophy 12, MIM# 618977
Mendeliome v0.3864 AFG3L2 Zornitza Stark Mode of inheritance for gene: AFG3L2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3863 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29181157, 26539208, 30252181, 30389403, 32219868, 32600459, 32548275; Phenotypes: Spastic ataxia 5, autosomal recessive (MIM#614487), Spinocerebellar ataxia 28 (MIM#610246), Optic atrophy 12, MIM# 618977; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3862 MYOD1 Zornitza Stark gene: MYOD1 was added
gene: MYOD1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MYOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYOD1 were set to 26733463; 30403323; 31260566
Phenotypes for gene: MYOD1 were set to Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, MIM# 618975
Review for gene: MYOD1 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Mendeliome v0.3860 TMEM237 Zornitza Stark Mode of inheritance for gene: TMEM237 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3857 NOD2 Zornitza Stark Mode of inheritance for gene: NOD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3856 NOD2 Zornitza Stark reviewed gene: NOD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15459013; Phenotypes: Blau syndrome, MIM# 186580; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3854 PAX3 Zornitza Stark Mode of inheritance for gene: PAX3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3853 KANSL1 Zornitza Stark reviewed gene: KANSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22544363; Phenotypes: Koolen-De Vries syndrome (MIM#610443); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3851 KANSL1 Zornitza Stark Mode of inheritance for gene: KANSL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3850 PAX3 Michelle Torres reviewed gene: PAX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301703, 30854529; Phenotypes: Craniofacial-deafness-hand syndrome (MIM#122880), AD 2, Rhabdomyosarcoma 2, alveolar (MIM#268220), SMu, Waardenburg syndrome, type 1 (MIM#193500), AD, Waardenburg syndrome, type 3 (MIM#148820), AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3850 KANSL1 Michelle Torres reviewed gene: KANSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Koolen-De Vries syndrome (MIM#610443); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3850 ESRRB Zornitza Stark Phenotypes for gene: ESRRB were changed from to Deafness, autosomal recessive 35, MIM#608565
Mendeliome v0.3848 ESRRB Zornitza Stark Mode of inheritance for gene: ESRRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3847 ESRRB Zornitza Stark reviewed gene: ESRRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179891, 31389194, 32681043; Phenotypes: Deafness, autosomal recessive 35, MIM#608565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3846 HNRNPA2B1 Zornitza Stark gene: HNRNPA2B1 was added
gene: HNRNPA2B1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPA2B1 were set to 23455423; 30279180; 29358076; 26744327; 23635965
Phenotypes for gene: HNRNPA2B1 were set to Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 MIM#615422
Review for gene: HNRNPA2B1 was set to AMBER
Added comment: One family reported that segregates cognitive impairment as part of the phenotype, and extensive functional analysis of protein, including a drosophila model.
Sources: Literature
Mendeliome v0.3844 PSMC3 Zornitza Stark gene: PSMC3 was added
gene: PSMC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC3 were set to 32500975
Phenotypes for gene: PSMC3 were set to Deafness; cataract
Review for gene: PSMC3 was set to AMBER
Added comment: Three affected individuals from a single consanguineous family reported with homozygous intronic variant. Animal model.
Sources: Literature
Mendeliome v0.3840 SOS2 Zornitza Stark Mode of inheritance for gene: SOS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3839 SOS2 Chern Lim reviewed gene: SOS2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 26173643; Phenotypes: Noonan syndrome 9, MIM#616559, AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.3838 NCKAP1L Zornitza Stark reviewed gene: NCKAP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 72 with autoinflammation 618982; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3836 RAI1 Zornitza Stark Mode of inheritance for gene: RAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3835 RAI1 Kristin Rigbye reviewed gene: RAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 11404004, 12652298, 15788730; Phenotypes: Smith-Magenis syndrome (MIM#182290), AD, IC; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3834 TAF1C Zornitza Stark gene: TAF1C was added
gene: TAF1C was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology
Review for gene: TAF1C was set to AMBER
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants. Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual). Following a normal CMA, exome in the first case revealed a homozygous missense SNV (NM_005679.3:c.1165C>T / p.Arg389Cys) supported by in silico predictions. mRNA and protein levels were substantially reduced in fibroblasts from this subject. Only the patient and parents were tested for the variant but not 3 unaffected sibs (fig1). The second individual was homozygous for another missense variant (p.Arg405Cys) also supported by in silico predictions. The girl was the single affected person within the family with an unaffected sib and parents heterozygous for the variant. Several other unaffected relatives in the extended pedigree were either carriers for this variant or homozygous for the wt allele. TAF1C encodes the TATA-box binding protein associated factor (TAF) RNA polymerase I subunit. RNA polymerase I (Pol I) transcribes genes to produce rRNA. For Pol I to initiate transcription, two transcription factors are required : UBF (upstream binding factor encoded by UBTF) and SL1 (selectivity factor 1). The latter is formed by TBP (TATA-binding protein) and 3 Pol I-specific TBP-associated factors (TAFs). A recurrent de novo missense variant in UBTF (encoding the other Pol I transcription factor) causes a disorder with highly similar features. The specific variant acts through a gain-of-function mechanism (and not by LoF which appears to apply for TAF1C based on expression data). The authors hypothesize that altered Pol I activity and resulting ribosomal stress could cause the microcephaly and leukodystrophy (both reported in 1 - the same - individual).
Sources: Expert list
Mendeliome v0.3831 KALRN Zornitza Stark Mode of inheritance for gene: KALRN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3829 KALRN Zornitza Stark reviewed gene: KALRN: Rating: RED; Mode of pathogenicity: None; Publications: 17357071, 27421267, 30675382, 32580138; Phenotypes: Susceptibility to coronary heart disease, Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3827 KRT6C Zornitza Stark Mode of inheritance for gene: KRT6C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3826 KRT6C Zornitza Stark reviewed gene: KRT6C: Rating: GREEN; Mode of pathogenicity: None; Publications: 31823354; Phenotypes: Palmoplantar keratoderma, nonepidermolytic, focal or diffuse (MIM#615735); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3824 KRT6B Zornitza Stark Mode of inheritance for gene: KRT6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3823 KRT6B Zornitza Stark reviewed gene: KRT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31823354; Phenotypes: Pachyonychia congenita 4 (MIM#615728); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3821 KRT2 Zornitza Stark Mode of inheritance for gene: KRT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3820 KRT2 Zornitza Stark reviewed gene: KRT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26581228, 22612346; Phenotypes: Superficial epidermolytic ichthyosis (SEI) (MIM#146800); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3818 KRT17 Zornitza Stark Mode of inheritance for gene: KRT17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3817 KRT17 Zornitza Stark reviewed gene: KRT17: Rating: GREEN; Mode of pathogenicity: None; Publications: 31823354; Phenotypes: Pachyonychia congenita 2, MIM#167210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3815 SERPINB7 Zornitza Stark Mode of inheritance for gene: SERPINB7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3814 SERPINB7 Zornitza Stark reviewed gene: SERPINB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 24773080, 24207119, 24514002, 31706940; Phenotypes: Palmoplantar keratoderma, Nagashima type (MIM#615598); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3812 SLURP1 Zornitza Stark Mode of inheritance for gene: SLURP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3811 SLURP1 Zornitza Stark changed review comment from: Over 10 families reported with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma, keratotic skin lesions, perioral erythema, brachydactyly, and nail abnormalities.; to: Over 10 families reported with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma, keratotic skin lesions, perioral erythema, brachydactyly, and nail abnormalities. Note single report of manifesting carriers.
Mendeliome v0.3811 SLURP1 Zornitza Stark edited their review of gene: SLURP1: Changed publications: 14674887, 32157724, 12483299, 14756676; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3811 SLURP1 Zornitza Stark reviewed gene: SLURP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14674887, 32157724, 12483299; Phenotypes: Meleda disease (MIM#248300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3808 ACTN4 Zornitza Stark Mode of inheritance for gene: ACTN4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3807 VKORC1 Zornitza Stark Mode of inheritance for gene: VKORC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3806 VKORC1 Zornitza Stark reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14765194, 21900891, 28198005; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM# 607473, Warfarin resistance, MIM# 122700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3806 ACTN4 Elena Savva reviewed gene: ACTN4: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26740551, 22351778, 10700177, 26301083; Phenotypes: Glomerulosclerosis, focal segmental, 1, 603278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3805 TPM4 Zornitza Stark gene: TPM4 was added
gene: TPM4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TPM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TPM4 were set to 28134622; 31249973; 21153663
Phenotypes for gene: TPM4 were set to Macrothrombocytopaenia
Review for gene: TPM4 was set to GREEN
Added comment: Three families reported in addition to genome-wide association studies in nearly 70,000 individuals which indicate that SNVs in TPM4 exert an effect on the count and volume of platelets.
Sources: Expert list
Mendeliome v0.3802 THPO Zornitza Stark Mode of inheritance for gene: THPO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3801 THPO Zornitza Stark reviewed gene: THPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 9425899, 10583217; Phenotypes: Thrombocythemia 1, MIM# 187950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3798 TBXAS1 Zornitza Stark Mode of inheritance for gene: TBXAS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3797 TBXAS1 Zornitza Stark reviewed gene: TBXAS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18264100; Phenotypes: Ghosal hematodiaphyseal syndrome, MIM# 231095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3796 SRC Zornitza Stark gene: SRC was added
gene: SRC was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SRC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRC were set to 31204551; 26936507
Phenotypes for gene: SRC were set to Thrombocytopaenia 6, MIM# 616937
Review for gene: SRC was set to GREEN
Added comment: Two families, and convincing functional data including animal model.
Sources: Expert list
Mendeliome v0.3794 SLFN14 Zornitza Stark gene: SLFN14 was added
gene: SLFN14 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLFN14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLFN14 were set to 26280575; 26769223
Phenotypes for gene: SLFN14 were set to Bleeding disorder, platelet-type, 20, MIM# 616913
Review for gene: SLFN14 was set to GREEN
Added comment: At least four unrelated families reported.
Sources: Expert list
Mendeliome v0.3792 PTPRJ Zornitza Stark gene: PTPRJ was added
gene: PTPRJ was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PTPRJ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPRJ were set to 30591527
Phenotypes for gene: PTPRJ were set to Thrombocytopaenia
Review for gene: PTPRJ was set to AMBER
Added comment: Two siblings reported with nonsyndromic thrombocytopenia characterised by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. Supportive zebrafish model.
Sources: Expert list
Mendeliome v0.3790 PTGS1 Zornitza Stark gene: PTGS1 was added
gene: PTGS1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PTGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTGS1 were set to 32299908; 11442478; 27629384; 8562397
Phenotypes for gene: PTGS1 were set to Platelet dysfunction; bleeding
Review for gene: PTGS1 was set to AMBER
Added comment: Single molecularly characterised family reported. However, note at least two previous older reports where deficiency was identified at protein rather than gene level.
Sources: Expert list
Mendeliome v0.3789 PRKACG Zornitza Stark gene: PRKACG was added
gene: PRKACG was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PRKACG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKACG were set to 25061177; 30819905
Phenotypes for gene: PRKACG were set to Bleeding disorder, platelet-type, 19, MIM# 616176
Review for gene: PRKACG was set to RED
Added comment: Single family reported only. A heterozygous VOUS reported in another individual in PMID 30819905 together with several other VOUS in same individual.
Sources: Expert list
Mendeliome v0.3787 PLAU Zornitza Stark gene: PLAU was added
gene: PLAU was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLAU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLAU were set to 20007542
Phenotypes for gene: PLAU were set to Quebec platelet disorder, MIM# 601709
Review for gene: PLAU was set to GREEN
Added comment: Note this is a tandem 78kb duplication of the gene, multiple families reported.
Sources: Expert list
Mendeliome v0.3785 PLA2G4A Zornitza Stark gene: PLA2G4A was added
gene: PLA2G4A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLA2G4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLA2G4A were set to 18451993; 25102815; 23268370
Phenotypes for gene: PLA2G4A were set to Gastrointestinal ulceration, recurrent, with dysfunctional platelets, MIM# 618372
Review for gene: PLA2G4A was set to GREEN
Added comment: At least three unrelated individuals reported.
Sources: Expert list
Mendeliome v0.3783 MPIG6B Zornitza Stark gene: MPIG6B was added
gene: MPIG6B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MPIG6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPIG6B were set to 31276734; 29898956; 27743390
Phenotypes for gene: MPIG6B were set to Thrombocytopenia, anemia, and myelofibrosis, MIM# 617441
Review for gene: MPIG6B was set to GREEN
Added comment: Six families reported.
Sources: Expert list
Mendeliome v0.3780 MAT2A Zornitza Stark Mode of inheritance for gene: MAT2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3778 MAT2A Zornitza Stark reviewed gene: MAT2A: Rating: AMBER; Mode of pathogenicity: None; Publications: 30071989, 25557781; Phenotypes: Thoracic aortic aneurysm; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3776 LOX Zornitza Stark Mode of inheritance for gene: LOX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3775 LOX Zornitza Stark reviewed gene: LOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 26838787, 30675029; Phenotypes: Aortic aneurysm, familial thoracic 10, MIM# 617168; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3773 KDSR Zornitza Stark Mode of inheritance for gene: KDSR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3772 KDSR Zornitza Stark reviewed gene: KDSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 28774589, 30467204, 28575652; Phenotypes: Erythrokeratodermia variabilis et progressiva 4, MIM# 617526, severe thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3770 GGCX Zornitza Stark Mode of inheritance for gene: GGCX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3769 GGCX Zornitza Stark reviewed gene: GGCX: Rating: GREEN; Mode of pathogenicity: None; Publications: 32785662, 30531603, 26758921; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 1, MIM# 277450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3767 GPI Zornitza Stark Mode of inheritance for gene: GPI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3766 GPI Zornitza Stark reviewed gene: GPI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemolytic anemia, nonspherocytic, due to glucose phosphate isomerase deficiency, MIM# 613470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3764 KANK2 Zornitza Stark Mode of inheritance for gene: KANK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3763 KANK2 Zornitza Stark reviewed gene: KANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25961457, 24671081; Phenotypes: Palmoplantar keratoderma and woolly hair (MIM#616099), Nephrotic syndrome, type 16, MIM#617783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3763 FAM83G Zornitza Stark gene: FAM83G was added
gene: FAM83G was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAM83G was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM83G were set to 29138053
Phenotypes for gene: FAM83G were set to Palmoplantar keratoderma, curly scalp hair and toenail dystrophy
Review for gene: FAM83G was set to RED
Added comment: PMID: 29138053; - 2 siblings born of consanguineous family presented with palmoplantar keratoderma and exuberant curly scalp hair - progressive development of yellowish thickened scaly skin affecting the palms and soles since 2 years of age, and toenail dystrophy in their teenage years > homozygous for a missense p.(Ala34Glu)
Sources: Expert list
Mendeliome v0.3759 CAST Zornitza Stark Mode of inheritance for gene: CAST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3758 CAST Zornitza Stark reviewed gene: CAST: Rating: GREEN; Mode of pathogenicity: None; Publications: 25683118, 31392520, 30656735, 28851602; Phenotypes: Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (MIM#616295); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3756 CARD14 Zornitza Stark Mode of inheritance for gene: CARD14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3755 CARD14 Zornitza Stark reviewed gene: CARD14: Rating: GREEN; Mode of pathogenicity: None; Publications: 22703878, 27760266; Phenotypes: Pityriasis rubra pilaris (MIM#173200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3753 TRPV3 Zornitza Stark Mode of inheritance for gene: TRPV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3752 TRPV3 Zornitza Stark reviewed gene: TRPV3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25285920, 22405088, 24452206; Phenotypes: Olmsted syndrome, MIM# 614594; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3750 EPHB2 Zornitza Stark Mode of inheritance for gene: EPHB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3748 EPHB2 Zornitza Stark reviewed gene: EPHB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30213874, 25370417; Phenotypes: Bleeding disorder, platelet-type, 22, MIM# 618462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3746 ACTN1 Zornitza Stark Mode of inheritance for gene: ACTN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3745 ACTN1 Zornitza Stark reviewed gene: ACTN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23434115; Phenotypes: Bleeding disorder, platelet-type, 15, MIM# 615193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3745 DSG3 Zornitza Stark gene: DSG3 was added
gene: DSG3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DSG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSG3 were set to 30528827
Phenotypes for gene: DSG3 were set to Mucosal blistering
Review for gene: DSG3 was set to RED
Added comment: One individual with recurrent blisters and erosions in the oral mucosa since birth homozygous for p(.R287*).
Sources: Expert list
Mendeliome v0.3743 CSTB Ain Roesley reviewed gene: CSTB: Rating: AMBER; Mode of pathogenicity: None; Publications: 28457472; Phenotypes: Keratolytic winter erythema (MIM#148370); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3743 ATP2C1 Ain Roesley reviewed gene: ATP2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28551824; Phenotypes: Hailey-Hailey disease (MIM# 169600); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3741 MADD Zornitza Stark Mode of inheritance for gene: MADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3740 MADD Zornitza Stark reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: Intellectual disability, seizures, autonomic dysfunction, endocrine dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3738 UNC45A Zornitza Stark Mode of inheritance for gene: UNC45A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3737 UNC45A Zornitza Stark reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429573; Phenotypes: Cholestasis, Diarrhoea, Bone fragility, Impaired hearing; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3734 HFE2 Zornitza Stark Mode of inheritance for gene: HFE2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3733 HFE2 Zornitza Stark reviewed gene: HFE2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemochromatosis, type 2A, MIM# 602390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3732 FAM50A Zornitza Stark gene: FAM50A was added
gene: FAM50A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FAM50A were set to 32703943
Phenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)
Review for gene: FAM50A was set to GREEN
Added comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).
Sources: Literature
Mendeliome v0.3729 ADK Zornitza Stark Mode of inheritance for gene: ADK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3728 ADK Zornitza Stark reviewed gene: ADK: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963049, 17120046; Phenotypes: Hypermethioninemia due to adenosine kinase deficiency, MIM# 614300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3728 SGK3 Zornitza Stark gene: SGK3 was added
gene: SGK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGK3 were set to 31821448
Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets
Review for gene: SGK3 was set to RED
Added comment: 5 individuals from one family where a splice site variant segregated with disease.
Sources: Literature
Mendeliome v0.3725 SEC24D Zornitza Stark Mode of inheritance for gene: SEC24D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3724 SEC24D Zornitza Stark reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: None; Publications: 30462379, 27942778, 26467156, 25683121; Phenotypes: Cole-Carpenter syndrome 2, MIM# 616294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3722 P4HB Zornitza Stark Mode of inheritance for gene: P4HB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3721 P4HB Zornitza Stark reviewed gene: P4HB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30063094, 29263160, 25683117, 29384951; Phenotypes: Cole-Carpenter syndrome 1, MIM#112240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3721 MPDZ Zornitza Stark Phenotypes for gene: MPDZ were changed from to Hydrocephalus, congenital, 2, with or without brain or eye anomalies, MIM# 615219
Mendeliome v0.3719 MPDZ Zornitza Stark Mode of inheritance for gene: MPDZ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3718 MPDZ Zornitza Stark reviewed gene: MPDZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 28556411, 23240096, 30518636, 29499638; Phenotypes: Hydrocephalus, congenital, 2, with or without brain or eye anomalies, MIM# 615219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3716 B3GNT2 Zornitza Stark Mode of inheritance for gene: B3GNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3714 B3GNT2 Zornitza Stark edited their review of gene: B3GNT2: Added comment: Gene previously known as B3GNT1. Two families reported.; Changed rating: AMBER; Changed publications: 23359570, 23877401; Changed phenotypes: Muscular dystrophy-dystroglycanopathy; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3713 SOX6 Zornitza Stark reviewed gene: SOX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tolchin-Le Caignec syndrome, MIM#618971; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3713 CNTN2 Zornitza Stark gene: CNTN2 was added
gene: CNTN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNTN2 were set to 23518707
Phenotypes for gene: CNTN2 were set to Epilepsy
Review for gene: CNTN2 was set to RED
Added comment: Single family reported in 2013, supportive mouse model.
Sources: Literature
Mendeliome v0.3711 DNAH8 Zornitza Stark edited their review of gene: DNAH8: Added comment: Four additional individuals with sperm morphological abnormalities and male infertility reported.; Changed rating: GREEN; Changed publications: 31178125, 24307375, 32619401, 32681648
Mendeliome v0.3709 DTNA Zornitza Stark Mode of inheritance for gene: DTNA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3707 DTNA Zornitza Stark reviewed gene: DTNA: Rating: RED; Mode of pathogenicity: None; Publications: 29118297, 11238270, 16427346; Phenotypes: Left ventricular noncompaction 1, with or without congenital heart defects, MIM# 604169; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3707 HYLS1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Amber/Green and mechanism unclear. However, given at least two variants reported with a ciliopathy phenotype and supporting functional data from multiple animal models all indicative of ciliopathy, keep Green.
Mendeliome v0.3704 HYLS1 Zornitza Stark Mode of inheritance for gene: HYLS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3703 HYLS1 Melanie Marty reviewed gene: HYLS1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 15843405, 18648327, 19400947, 19656802, 32509774; Phenotypes: Hydrolethalus syndrome (MIM#236680); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3703 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (MIM#618577), AD to Mental retardation, autosomal dominant 48, MIM# 617751
Mendeliome v0.3702 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (MIM#618577), AD
Mendeliome v0.3699 RAC1 Zornitza Stark Mode of inheritance for gene: RAC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3698 RAC1 Kristin Rigbye reviewed gene: RAC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30042656, 29276006, 30293988; Phenotypes: Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (MIM#618577), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3697 FANCD2 Zornitza Stark Mode of inheritance for gene: FANCD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3696 FANCD2 Michelle Torres reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group D2, MIM#227646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3694 BCOR Zornitza Stark Mode of inheritance for gene: BCOR was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3693 BCOR Zornitza Stark reviewed gene: BCOR: Rating: GREEN; Mode of pathogenicity: None; Publications: 29974297; Phenotypes: Microphthalmia, syndromic 2, MIM# 300166, Oculofaciocardiodental syndrome, Lenz microphthalmia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3692 NKX2-5 Dean Phelan reviewed gene: NKX2-5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30354339, 28690296, 25503402, 27855642; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3692 ARSE Zornitza Stark Mode of inheritance for gene: ARSE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3690 ARSE Zornitza Stark reviewed gene: ARSE: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chondrodysplasia punctata, X-linked recessive, MIM# 302950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3690 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from to Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Spinocerebellar ataxia, autosomal recessive 7, MIM# 609270
Mendeliome v0.3688 TPP1 Zornitza Stark Mode of inheritance for gene: TPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3685 PSAT1 Zornitza Stark Mode of inheritance for gene: PSAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3684 TPP1 Michelle Torres reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31283065; Phenotypes: Ceroid lipofuscinosis, neuronal, 2 204500, Spinocerebellar ataxia, autosomal recessive 7 609270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3684 PSAT1 Elena Savva reviewed gene: PSAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32077105; Phenotypes: ?Phosphoserine aminotransferase deficiency 610992, Neu-Laxova syndrome 2 616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3684 FBXO11 Zornitza Stark Phenotypes for gene: FBXO11 were changed from to Intellectual Developmental Disorder with Dysmorphic Facies and Behavioural Abnormalities, MIM#618089
Mendeliome v0.3682 FBXO11 Zornitza Stark Mode of inheritance for gene: FBXO11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3681 FBXO11 Zornitza Stark reviewed gene: FBXO11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30679813, 30057029, 29796876; Phenotypes: Intellectual Developmental Disorder with Dysmorphic Facies and Behavioural Abnormalities, MIM#618089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3679 FRMD7 Zornitza Stark Mode of inheritance for gene: FRMD7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3676 AIFM1 Zornitza Stark Mode of inheritance for gene: AIFM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3675 FRMD7 Elena Savva reviewed gene: FRMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19072571, 23406872; Phenotypes: Nystagmus 1, congenital, X-linked 310700, Nystagmus, infantile periodic alternating, X-linked 310700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.3675 AIFM1 Elena Savva reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28842795; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3675 PIGQ Zornitza Stark edited their review of gene: PIGQ: Added comment: Homozygous or compound heterozygous mutations in PIGQ cause Epileptic encephalopathy, early infantile, 77 (MIM #618548).

Johnstone et al (2020 - PMID: 32588908) describe the phenotype of 7 children (from 6 families) with biallelic PIGQ pathogenic variants. The authors also review the phenotype of 3 subjects previously reported in the literature (by Martin et al, Alazami et al, Starr et al - respective PMIDs: 24463883, 25558065, 31148362).

Affected individuals displayed severe to profound global DD/ID and seizures with onset in the first year of life. There were variable other features incl. - among others - genitourinary, cardiac, skeletal, ophthalmological anomalies, gastrointestinal issues. Within the cohort there was significant morbidity/mortality.

PIGQ encodes phosphatidylinositol glycan anchor biosynthesis class Q protein, playing a role (early) in the biosynthesis of the GPI-anchor. Several genes in the GPI biosynthesis pathway cause multi-system disease with DD/ID and seizures. Flow cytometry has been used in individuals with PIGQ-related disorder. Serum ALP was elevated in some (4) although - as the authors comment - elevations are more typical in disorders affecting later steps of GPI biosynthesis.

More than 10 variants have been reported to date (missense / pLoF).; Changed phenotypes: Epileptic encephalopathy, early infantile, 77, MIM# 618548
Mendeliome v0.3673 SEC61B Zornitza Stark gene: SEC61B was added
gene: SEC61B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SEC61B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61B were set to 28862642; 30652979; 28375157
Phenotypes for gene: SEC61B were set to Polycystic liver disease with or without renal cysts
Review for gene: SEC61B was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert list
Mendeliome v0.3669 C3orf52 Zornitza Stark gene: C3orf52 was added
gene: C3orf52 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C3orf52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C3orf52 were set to 32336749
Phenotypes for gene: C3orf52 were set to Localized hypotrichosis
Review for gene: C3orf52 was set to AMBER
Added comment: 2 families with 4 individuals with localised hypotrichosis and homozygous variants in C3ORF52. C3ORF52 was found to be coexpressed with lipase H in the inner root sheath of the hair follicle and the two proteins were found to directly interact. The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H–mediated 2-acyl-lysophosphatidic acid (LPA) biosynthesis. Same pathway as two other genes for localised hypotrichosis (LIPH and LPAR6)
Sources: Literature
Mendeliome v0.3668 NDUFA8 Zornitza Stark gene: NDUFA8 was added
gene: NDUFA8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDUFA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA8 were set to 32385911
Phenotypes for gene: NDUFA8 were set to NDUFA8-related mitochondrial disease; Developmental delay; microcehaly; seizures
Review for gene: NDUFA8 was set to RED
Added comment: Single individual reported with homozygous variant, fibroblasts showed apparent biochemical defects in mitochondrial complex I.
Sources: Literature
Mendeliome v0.3666 DLG5 Zornitza Stark gene: DLG5 was added
gene: DLG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816
Phenotypes for gene: DLG5 were set to Cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations
Review for gene: DLG5 was set to GREEN
Added comment: Four unrelated families reported, supportive Xenopus animal model data.
Sources: Literature
Mendeliome v0.3662 RELN Zornitza Stark edited their review of gene: RELN: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3659 RELN Zornitza Stark Mode of inheritance for gene: RELN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3658 RELN Zornitza Stark reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 2 (Norman-Roberts type), MIM# 257320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3657 CALCRL Hazel Phillimore gene: CALCRL was added
gene: CALCRL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CALCRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CALCRL were set to PMID: 30115739
Phenotypes for gene: CALCRL were set to ?Lymphatic malformation 8 (MIM# 618773); hydrops fetalis
Review for gene: CALCRL was set to RED
Added comment: Homozygous in-frame deletion (Val205del) in the CALCRL gene (Val205del) in a 22 week-old fetus with hydrops details due to lymphatic malformation. Consanguineous parents.
Heterozygosity of the variant was also suggested to be associated with spontaneous miscarriage and subfertility. Consanguineous family with 8 total miscarriages from 3 carrier women, and 2 of these were confirmed to be due to hydrops fetalis.
Note: possible association of a variant in ASAH1 gene that is associated with Farber lipogranulomatosis which can sometimes present with antenatal hydrops fetalis. (Homozygosity in one of the fetuses, fetus and heterozygosity in some of the family members).
In vitro biochemical assays indicated that the variant causes misfolding of the protein and reduced association with its chaperone, RAMP2, and reduced translocation to the plasma membrane. (PMID: 30115739; Mackie, DI. et al., 2018).
Sources: Literature
Mendeliome v0.3657 RELN Chern Lim reviewed gene: RELN: Rating: AMBER; Mode of pathogenicity: None; Publications: 32001840; Phenotypes: ankylosing spondylitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3657 MORC2 Dean Phelan reviewed gene: MORC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32693025; Phenotypes: Spinal muscular atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3657 M1AP Ee Ming Wong gene: M1AP was added
gene: M1AP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: M1AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: M1AP were set to PMID: 32673564
Phenotypes for gene: M1AP were set to non-obstructive azoospermia (NOA); severe spermatogenic failure; male infertility
Review for gene: M1AP was set to GREEN
gene: M1AP was marked as current diagnostic
Added comment: - One frameshift variant identified in 9 infertile men either in homozygous or compound heterozygous form
- One missense variant segregated with infertility in five men from a consanguineous Turkish family
Sources: Literature
Mendeliome v0.3657 AHR Chern Lim gene: AHR was added
gene: AHR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AHR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHR were set to 29726989; 31896775
Phenotypes for gene: AHR were set to ?Retinitis pigmentosa 85 MIM#618345; foveal hypoplasia and infantile nystagmus
Review for gene: AHR was set to AMBER
Added comment: - One reported homozygous splice variant in a consanguineous family & a mouse model (PMID: 29726989)

- A homozygous nonsense variant in 1 consanguineous family with foveal hypoplasia and infantile nystagmus (PMID:31896775).
Sources: Literature
Mendeliome v0.3656 FBXL7 Zornitza Stark Phenotypes for gene: FBXL7 were changed from Hennekam lymphangiectasia-lymphedema syndrome; lymphedema; protein‐losing enteropathy; dental anomalies; camptodactyly; microtia; small auditory canals; ductive hearing loss; middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae. to Hennekam lymphangiectasia-lymphedema syndrome
Mendeliome v0.3653 CRY1 Ee Ming Wong gene: CRY1 was added
gene: CRY1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRY1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRY1 were set to PMID: 28388406; PMID: 32538895
Phenotypes for gene: CRY1 were set to Attention deficit/hyperactivity disorder (ADHD); Delayed sleep phase disorder (DSPD),
Penetrance for gene: CRY1 were set to Incomplete
Review for gene: CRY1 was set to GREEN
gene: CRY1 was marked as current diagnostic
Added comment: - Splice variants identified in 7 families with ADHD and DSPD
- Gain of function suggested for CRY1Δ11 (PMID: 28388406)
- Loss of function suggested for CRY1Δ6 (HEK293T cells transfected with a Per1::Luc reporter plasmid showed reduced repressor activity compared to WT and CRY1Δ11)
Sources: Literature
Mendeliome v0.3649 PIGP Seb Lunke reviewed gene: PIGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 32042915; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3648 FBXL7 Hazel Phillimore changed review comment from: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature; to: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Mendeliome v0.3647 FBXL7 Hazel Phillimore gene: FBXL7 was added
gene: FBXL7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL7 were set to PMID: 31633297
Phenotypes for gene: FBXL7 were set to Hennekam lymphangiectasia-lymphedema syndrome; lymphedema; protein‐losing enteropathy; dental anomalies; camptodactyly; microtia; small auditory canals; ductive hearing loss; middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Review for gene: FBXL7 was set to AMBER
Added comment: Homozygous deletion of exon 3 of FBXL7 (predicted to be in-frame) in a 2-year old with novel form of Hennekam syndrome. Each parent was heterozygous.
Patient had lymphedema, protein‐losing enteropathy, dental anomalies, camptodactyly, microtia, small auditory canals, ductive hearing loss, middle ear anomalies, bifid scrotum, and facial dysmorphic features including hypertelorism, telecanthus, epicanthal folds, downslanting palpebral fissures, broad and depressed nasal bridge, and thickened nasal alae.
Sources: Literature
Mendeliome v0.3647 HPDL Crystle Lee gene: HPDL was added
gene: HPDL was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurological disorder
Review for gene: HPDL was set to GREEN
Added comment: Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia
Sources: Expert Review
Mendeliome v0.3646 PJA1 Zornitza Stark gene: PJA1 was added
gene: PJA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PJA1 were set to 32530565
Phenotypes for gene: PJA1 were set to Intellectual disability; trigonocephaly
Review for gene: PJA1 was set to AMBER
Added comment: Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect
Sources: Literature
Mendeliome v0.3645 MYLPF Crystle Lee gene: MYLPF was added
gene: MYLPF was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLPF were set to 32707087
Phenotypes for gene: MYLPF were set to Distal arthrogryoposis
Review for gene: MYLPF was set to GREEN
Added comment: 2 different homozygous variants reported in 6 consanguineous families with DA and an additional 2 different dominantly inherited variants in 2 families, with supporting animal model.
Sources: Expert Review
Mendeliome v0.3645 NCKAP1L Michelle Torres gene: NCKAP1L was added
gene: NCKAP1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCKAP1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCKAP1L were set to 32647003
Phenotypes for gene: NCKAP1L were set to Immunodeficiency
Review for gene: NCKAP1L was set to GREEN
Added comment: 5 patients from 4 families with recurrent bacterial and viral skin infections, severe respiratory tract infections leading to pneumonia and bronchiectasis. Functional of the 4 missense reported were performed.
Sources: Literature
Mendeliome v0.3645 MCF2 Zornitza Stark gene: MCF2 was added
gene: MCF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCF2 were set to 31846234
Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria
Review for gene: MCF2 was set to RED
Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model.
Sources: Literature
Mendeliome v0.3644 SCAF4 Crystle Lee gene: SCAF4 was added
gene: SCAF4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCAF4 were set to 32730804
Phenotypes for gene: SCAF4 were set to Mild intellectual disability; seizures; behavioral abnormalities
Review for gene: SCAF4 was set to GREEN
Added comment: > 5 variants reported in individuals with variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies.
Sources: Expert Review
Mendeliome v0.3643 NARS Zornitza Stark gene: NARS was added
gene: NARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225
Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Review for gene: NARS was set to GREEN
Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).
Sources: Literature
Mendeliome v0.3640 ZNF407 Zornitza Stark Mode of inheritance for gene: ZNF407 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3638 ZNF407 Zornitza Stark reviewed gene: ZNF407: Rating: AMBER; Mode of pathogenicity: None; Publications: 24907849, 32737394, 23195952; Phenotypes: Global developmental delay, Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3636 DDX58 Zornitza Stark Mode of inheritance for gene: DDX58 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3635 DDX58 Zornitza Stark changed review comment from: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.; to: Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies. At least 3 families reported.
Mendeliome v0.3635 DDX58 Zornitza Stark reviewed gene: DDX58: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620203; Phenotypes: Singleton-Merten syndrome 2, MIM# 616298; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3634 IVNS1ABP Zornitza Stark reviewed gene: IVNS1ABP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 70, MIM#618969; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3631 MAPK1 Zornitza Stark gene: MAPK1 was added
gene: MAPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Review for gene: MAPK1 was set to GREEN
Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants.

The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once.

MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway.

MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic).

The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome).
Sources: Literature
Mendeliome v0.3630 ASPM Zornitza Stark Phenotypes for gene: ASPM were changed from to Microcephaly 5, primary, autosomal recessive, MIM#608716
Mendeliome v0.3628 ASPM Zornitza Stark Mode of inheritance for gene: ASPM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3627 ASPM Elena Savva reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:29243349; Phenotypes: Microcephaly 5, primary, autosomal recessive, 608716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3626 AMBRA1 Bryony Thompson gene: AMBRA1 was added
gene: AMBRA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AMBRA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMBRA1 were set to 17589504; 32333458
Phenotypes for gene: AMBRA1 were set to Neural tube defects
Review for gene: AMBRA1 was set to GREEN
Added comment: 5 rare missense variants were identified in 6 cases from a neural tube defect cohort, and 4 (p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) of them were functionally validated to affect autophagy regulation in vitro or zebrafish embryo development in vivo. There is also null mouse model with neural tube defects.
Sources: Literature
Mendeliome v0.3624 ERLEC1 Bryony Thompson gene: ERLEC1 was added
gene: ERLEC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERLEC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERLEC1 were set to 32442352
Phenotypes for gene: ERLEC1 were set to Class III malocclusion
Review for gene: ERLEC1 was set to GREEN
Added comment: A heterozygous missense variant was found to co-segregate with dentofacial deformity in a multi-generational Chinese pedigree (2 unaffected carriers & 11 affected carriers), and 3 additional missense variants were identified in 3 unrelated cases from a sporadic malocclusion cohort. Additional functional assays were conducted to demonstrate that the proper level of ERLEC1 expression is crucial for proper osteogenic differentiation. All identified missense variants were assessed using luciferase reporter assays, and altered activity.
Sources: Literature
Mendeliome v0.3620 WDR1 Zornitza Stark Mode of inheritance for gene: WDR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3619 WDR1 Zornitza Stark reviewed gene: WDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27994071, 27557945, 29751004; Phenotypes: Periodic fever, immunodeficiency, and thrombocytopenia syndrome, MIM#150550, Neutropaenia, Poor wound healing, Severe stomatitis, Neutrophil nuclei herniate, Autoinflammatory periodic fever, Thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3618 KREMEN1 Bryony Thompson gene: KREMEN1 was added
gene: KREMEN1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KREMEN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KREMEN1 were set to 27049303; 27550540
Phenotypes for gene: KREMEN1 were set to Ectodermal dysplasia 13, hair/tooth type MIM#617392
Review for gene: KREMEN1 was set to AMBER
Added comment: 4 consanguineous Palestinian families segregating the same homozygous missense (Phe209Ser) with disease phenotype which includes hair abnormalities. Possible founder variant. There are also animal model functional assays that suggest the gene is involved in hair development.
Sources: Expert list
Mendeliome v0.3614 TUBB2A Zornitza Stark Phenotypes for gene: TUBB2A were changed from to Cortical dysplasia, complex, with other brain malformations 5 MIM#615763
Mendeliome v0.3612 TUBB2A Zornitza Stark Mode of inheritance for gene: TUBB2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3611 TUBB2A Zornitza Stark reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, MIM# 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3609 PMP22 Zornitza Stark Mode of inheritance for gene: PMP22 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3608 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1A, MIM# 118220, Charcot-Marie-Tooth disease, type 1E, MIM# 118300, Dejerine-Sottas disease, MIM# 145900, Neuropathy, recurrent, with pressure palsies 162500, Roussy-Levy syndrome 180800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3607 OTX2 Zornitza Stark Mode of inheritance for gene: OTX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3606 OTX2 Zornitza Stark reviewed gene: OTX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3604 CDAN1 Zornitza Stark Mode of inheritance for gene: CDAN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3601 NGLY1 Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3600 NGLY1 Zornitza Stark reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24651605, 27388694; Phenotypes: Congenital disorder of deglycosylation, MIM# 615273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3599 IMPG2 Zornitza Stark Mode of inheritance for gene: IMPG2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3596 IMPG2 Zornitza Stark Mode of inheritance for gene: IMPG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3594 EEF1A2 Zornitza Stark Mode of inheritance for gene: EEF1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3593 EEF1A2 Zornitza Stark Phenotypes for gene: EEF1A2 were changed from to Epileptic encephalopathy, early infantile, 33, MIM# 616409; Mental retardation, autosomal dominant 38, MIM# 616393
Mendeliome v0.3590 ANO1 Arina Puzriakova gene: ANO1 was added
gene: ANO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANO1 were set to 32487539
Added comment: PMID: 32487539 (2020) - Two affected sibs presenting in early infancy with impaired intestinal peristalsis, intestinal pneumatosis and dysmorphic features. Delayed motor and language development was reported in one sibling, however, the other sibling died at 5 months from cardiac arrest and therefore a psychomotor assessment was performed. Exome sequencing identified a homozygous truncating variant (c.897+3_897+6delAAGT, p.L300Vfs*58) in ANO1 which segregated with disease in the family. Functional data revealed that the variant led to lack of expression of functional TMEM16A in patient cells, which in turn abolished calcium-activated Cl- currents. Also supportive mouse model.
Sources: Literature
Mendeliome v0.3590 CDAN1 Arina Puzriakova reviewed gene: CDAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32518175; Phenotypes: Dyserythropoietic anemia, congenital, type Ia, 224120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3590 GNPNAT1 Arina Puzriakova gene: GNPNAT1 was added
gene: GNPNAT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPNAT1 were set to 32591345
Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia
Review for gene: GNPNAT1 was set to RED
Added comment: Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature
Mendeliome v0.3590 PKD1L1 Zornitza Stark Phenotypes for gene: PKD1L1 were changed from to Heterotaxy, visceral, 8, autosomal (MIM#617205)
Mendeliome v0.3588 PKD1L1 Zornitza Stark Mode of inheritance for gene: PKD1L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3587 PKD1L1 Zornitza Stark reviewed gene: PKD1L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616478, 30664273, 20080492, 31026592; Phenotypes: Heterotaxy, visceral, 8, autosomal (MIM#617205); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3586 IVNS1ABP Bryony Thompson gene: IVNS1ABP was added
gene: IVNS1ABP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IVNS1ABP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IVNS1ABP were set to 32499645
Phenotypes for gene: IVNS1ABP were set to Primary immunodeficiency
Review for gene: IVNS1ABP was set to GREEN
Added comment: 3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes.
Sources: Literature
Mendeliome v0.3584 PTPN2 Bryony Thompson gene: PTPN2 was added
gene: PTPN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN2 were set to 32499645; 27658548
Phenotypes for gene: PTPN2 were set to Lupus; arthritis; common variable immunodeficiency
Review for gene: PTPN2 was set to AMBER
Added comment: A single family with a proband diagnosed with CVID and arthiritis (among other features) with an intronic expression quantitative trait loci (eQTL) rs2847297-G in trans with a stopgain variant. The stopgain variant was also identified in the proband's mother, who was diagnosed with lupus. A Ptpn2 deficient mouse model also demonstrates an autoimmune phenotype.
Sources: Literature
Mendeliome v0.3582 SOCS1 Bryony Thompson gene: SOCS1 was added
gene: SOCS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOCS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOCS1 were set to 32499645; 10490099; 10490100
Phenotypes for gene: SOCS1 were set to Common variable immunodeficiency
Review for gene: SOCS1 was set to GREEN
Added comment: 2 unrelated families with truncating variants with supportive immunophenotyping of patient cells, and supporting null mouse models.
Sources: Literature
Mendeliome v0.3581 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities to Hepatic disease; Combined respiratory chain complex deficiencies; Hepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities; Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3580 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities, Combined oxidative phosphorylation deficiency 45, MIM#618951
Mendeliome v0.3579 TASP1 Zornitza Stark Phenotypes for gene: TASP1 were changed from Developmental delay; microcephaly; dysmorphic features; congenital abnormalities to Developmental delay; microcephaly; dysmorphic features; congenital abnormalities; Suleiman-El-Hattab syndrome, MIM#618950
Mendeliome v0.3578 TASP1 Zornitza Stark edited their review of gene: TASP1: Changed phenotypes: Developmental delay, microcephaly, dysmorphic features, congenital abnormalities, Suleiman-El-Hattab syndrome, MIM#618950
Mendeliome v0.3576 OXCT1 Zornitza Stark Mode of inheritance for gene: OXCT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3575 OXCT1 Zornitza Stark reviewed gene: OXCT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25778941, 10964512, 8751852, 23420214; Phenotypes: Succinyl CoA:3-oxoacid CoA transferase deficiency MIM#245050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3573 KCNJ1 Zornitza Stark Mode of inheritance for gene: KCNJ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3572 ZFYVE27 Zornitza Stark Phenotypes for gene: ZFYVE27 were changed from to Spastic paraplegia 33, autosomal dominant MIM#610244
Mendeliome v0.3570 ZFYVE27 Zornitza Stark Mode of inheritance for gene: ZFYVE27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3566 MYOZ2 Zornitza Stark Mode of inheritance for gene: MYOZ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3561 OBSCN Paul De Fazio gene: OBSCN was added
gene: OBSCN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OBSCN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914
Phenotypes for gene: OBSCN were set to Hypertrophic cardiomyopathy
Review for gene: OBSCN was set to RED
gene: OBSCN was marked as current diagnostic
Added comment: Limited evidence by ClinGen working group.

Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review).

No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically.
Sources: Literature
Mendeliome v0.3561 PDLIM3 Ain Roesley gene: PDLIM3 was added
gene: PDLIM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDLIM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDLIM3 were set to 30681346; 26455666; 20801532
Phenotypes for gene: PDLIM3 were set to Hypertrophic cardiomyopathy
Penetrance for gene: PDLIM3 were set to unknown
Added comment: PMID: 30681346;
LIMITED by ClinGen working group

PMID: 26455666;
1x proband with multi-exon deletion

PMID: 20801532;
1x proband het for a missense
Sources: Literature
Mendeliome v0.3561 TRIM63 Ain Roesley gene: TRIM63 was added
gene: TRIM63 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM63 were set to 30681346; 32451364
Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy
Penetrance for gene: TRIM63 were set to unknown
Review for gene: TRIM63 was set to GREEN
Added comment: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- segregated in 3 families
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature
Mendeliome v0.3561 MYOZ2 Paul De Fazio reviewed gene: MYOZ2: Rating: RED; Mode of pathogenicity: None; Publications: 17347475, 18591919, 28296734, 30681346, 22987565; Phenotypes: Cardiomyopathy, hypertrophic, 16 MIM#613838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.3561 KLF10 Paul De Fazio gene: KLF10 was added
gene: KLF10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLF10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KLF10 were set to 22234868
Phenotypes for gene: KLF10 were set to HCM
gene: KLF10 was marked as current diagnostic
Added comment: Curated by ClinGen and rated as limited evidence.

Misssense mutations reported in six unrelated individuals patients (two males/four females), with family history of HCM only reported for one individual (PMID: 22234868). No further reports in the literature.
Sources: Literature
Mendeliome v0.3561 KCNJ1 Elena Savva reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28630040; Phenotypes: Bartter syndrome, type 2, 241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3560 KRT71 Bryony Thompson gene: KRT71 was added
gene: KRT71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KRT71 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KRT71 were set to 14632181; 22592156; 19713490
Phenotypes for gene: KRT71 were set to ?Hypotrichosis 13, 615896
Review for gene: KRT71 was set to AMBER
Added comment: A single family with 3 affected members of a 3-generation Japanese family segregating a missense variant (F141C) with autosomal dominant woolly hair/hypotrichosis, with supporting functional assays and animal models.
Sources: Literature
Mendeliome v0.3557 ACADL Zornitza Stark Mode of inheritance for gene: ACADL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3555 ACADL Zornitza Stark reviewed gene: ACADL: Rating: RED; Mode of pathogenicity: None; Publications: 24591516, 31399326; Phenotypes: Pulmonary surfactant dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3555 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286
Mendeliome v0.3552 TWNK Zornitza Stark Mode of inheritance for gene: TWNK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3551 TWNK Elena Savva reviewed gene: TWNK: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32234020, 18593709; Phenotypes: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245, Perrault syndrome 5 616138, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3550 P2RX2 Zornitza Stark Phenotypes for gene: P2RX2 were changed from to Deafness, autosomal dominant 41, MIM# 608224
Mendeliome v0.3548 P2RX2 Zornitza Stark Mode of inheritance for gene: P2RX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3547 P2RX2 Zornitza Stark reviewed gene: P2RX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23345450, 24211385; Phenotypes: Deafness, autosomal dominant 41, MIM# 608224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3547 KCNQ4 Zornitza Stark Phenotypes for gene: KCNQ4 were changed from to Deafness, autosomal dominant 2A, MIM# 600101
Mendeliome v0.3545 KCNQ4 Zornitza Stark Mode of inheritance for gene: KCNQ4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3544 KCNQ4 Zornitza Stark reviewed gene: KCNQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10369879; Phenotypes: Deafness, autosomal dominant 2A, MIM# 600101; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3542 FLCN Zornitza Stark Mode of inheritance for gene: FLCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3541 FLCN Crystle Lee reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 17124507, 30586397, 31625278; Phenotypes: Birt-Hogg-Dube syndrome (MIM#135150), Pneumothorax, primary spontaneous (MIM#173600); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3539 KERA Zornitza Stark Phenotypes for gene: KERA were changed from to Cornea plana 2, autosomal recessive, MIM# 217300
Mendeliome v0.3537 KERA Zornitza Stark Mode of inheritance for gene: KERA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3536 KERA Zornitza Stark reviewed gene: KERA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23834557, 11726611, 10802664; Phenotypes: Cornea plana 2, autosomal recessive, MIM# 217300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3530 CPA1 Zornitza Stark Mode of inheritance for gene: CPA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3529 CPA1 Zornitza Stark reviewed gene: CPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23955596, 28497564, 28258133, 31005883; Phenotypes: Susceptibility to chronic pancreatitis, Hereditary pancreatitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3524 BMP10 Zornitza Stark gene: BMP10 was added
gene: BMP10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BMP10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP10 were set to 30578383
Phenotypes for gene: BMP10 were set to Pulmonary arterial hypertension
Review for gene: BMP10 was set to AMBER
Added comment: A truncating mutation and a predicted loss-of-function missense variant were identified in BMP10 in two severely affected sporadic PAH female patients.
Sources: Expert list
Mendeliome v0.3522 SMAD1 Zornitza Stark gene: SMAD1 was added
gene: SMAD1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SMAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD1 were set to 21898662; 23478097
Phenotypes for gene: SMAD1 were set to Pulmonary arterial hypertension
Review for gene: SMAD1 was set to AMBER
Added comment: One missense variant identified in a PAH case. Mouse model is consistent with pulmonary hypertension.
Sources: Expert list
Mendeliome v0.3521 BRAP Zornitza Stark gene: BRAP was added
gene: BRAP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAP were set to 30703135
Phenotypes for gene: BRAP were set to Pulmonary arterial hypertension
Review for gene: BRAP was set to RED
Added comment: A single BRAP missense variant in a Japanese family with PAH, with in vitro functional assays suggesting a gain-of-function.
Sources: Expert list
Mendeliome v0.3520 KLF2 Zornitza Stark gene: KLF2 was added
gene: KLF2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KLF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLF2 were set to 28188237
Phenotypes for gene: KLF2 were set to Pulmonary arterial hypertension
Review for gene: KLF2 was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.3518 ATP13A3 Zornitza Stark gene: ATP13A3 was added
gene: ATP13A3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP13A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP13A3 were set to 31798832; 30679663; 29650961
Phenotypes for gene: ATP13A3 were set to Pulmonary arterial hypertension
Review for gene: ATP13A3 was set to GREEN
Added comment: Three heterozygous frameshift variants, three stop gained, two splice region variants in ATP13A3, which are predicted to lead to loss of ATPase catalytic activity identified in idiopathic/familial PAH cases. Also one case with putative recessive inheritance reported. ATP13A3 mRNA expression is confirmed in primary PASMCs and endothelial cells where its loss hindered proliferation and enhanced apoptosis of endothelial cells, which is known as the initiation event of PAH.
Sources: Expert list
Mendeliome v0.3514 SMARCA2 Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3513 SMARCA2 Zornitza Stark reviewed gene: SMARCA2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 26468571, 32694869; Phenotypes: Nicolaides-Baraitser syndrome, MIM #601358, Blepharophimosis-intellectual disability syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3511 MORC2 Zornitza Stark Mode of inheritance for gene: MORC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3510 MORC2 Zornitza Stark reviewed gene: MORC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32693025, 26497905, 26659848; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3508 DBT Zornitza Stark Mode of inheritance for gene: DBT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3507 DBT Teresa Zhao reviewed gene: DBT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20570198; Phenotypes: Maple syrup urine disease, type II (MIM#248600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3507 PLCB3 Zornitza Stark gene: PLCB3 was added
gene: PLCB3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLCB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCB3 were set to 29122926
Phenotypes for gene: PLCB3 were set to Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961
Review for gene: PLCB3 was set to RED
Added comment: Single consanguineous family reported.
Sources: Expert list
Mendeliome v0.3506 ACOX1 Zornitza Stark Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Mendeliome v0.3504 ACOX1 Zornitza Stark Mode of inheritance for gene: ACOX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3503 ACOX1 Zornitza Stark reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32169171, 17458872; Phenotypes: Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470, Mitchell syndrome, MIM# 618960; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3503 MNS1 Zornitza Stark Phenotypes for gene: MNS1 were changed from Heterotaxy; male infertility to Heterotaxy; male infertility; Heterotaxy, visceral, 9, autosomal, with male infertility, MIM# 618948
Mendeliome v0.3502 MNS1 Zornitza Stark edited their review of gene: MNS1: Changed phenotypes: Heterotaxy, male infertility, Heterotaxy, visceral, 9, autosomal, with male infertility, MIM# 618948
Mendeliome v0.3500 MPL Zornitza Stark Mode of inheritance for gene: MPL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3499 SH2B3 Zornitza Stark Phenotypes for gene: SH2B3 were changed from to Predisposition to haematological malignancies
Mendeliome v0.3497 SH2B3 Zornitza Stark Mode of inheritance for gene: SH2B3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3496 SH2B3 Zornitza Stark changed review comment from: Germline variants reported in association with increased risk for haematological malignancies.; to: Germline variants reported in association with increased risk for haematological malignancies.
Mendeliome v0.3496 SH2B3 Zornitza Stark reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26457647, 23908464, 31102422, 31173385; Phenotypes: Predisposition to haematological malignancies; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3496 MPL Chern Lim reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 28955303, 26423830; Phenotypes: Myelofibrosis with myeloid metaplasia, somatic, MIM#2544503, Thrombocythemia 2, MIM#601977, AD, SMu, Thrombocytopenia, congenital amegakaryocytic, MIM#604498, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3494 HPD Zornitza Stark Mode of inheritance for gene: HPD was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3493 HPD Zornitza Stark reviewed gene: HPD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10942115, 17560158; Phenotypes: Hawkinsinuria (MIM#140350), AD, Tyrosinemia type III (MIM#276710), AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3491 FANCM Zornitza Stark Mode of inheritance for gene: FANCM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3489 FANCM Zornitza Stark reviewed gene: FANCM: Rating: AMBER; Mode of pathogenicity: None; Publications: 30075111, 29895858, 28837162; Phenotypes: Spermatogenic failure 28, MIM# 618086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3487 HDAC8 Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3486 HDAC8 Zornitza Stark reviewed gene: HDAC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 30614194, 24403048; Phenotypes: Cornelia de Lange syndrome 5, MIM# 300882; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3485 RBM8A Zornitza Stark Mode of inheritance for gene: RBM8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3484 RBM8A Zornitza Stark reviewed gene: RBM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopenia-absent radius syndrome, MIM# 274000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3482 RPL15 Zornitza Stark Mode of inheritance for gene: RPL15 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3481 RPL15 Zornitza Stark reviewed gene: RPL15: Rating: GREEN; Mode of pathogenicity: None; Publications: 23812780, 29599205; Phenotypes: Diamond-Blackfan anemia 12, MIM# 615550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3479 RPS28 Zornitza Stark Mode of inheritance for gene: RPS28 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3477 RPS28 Zornitza Stark reviewed gene: RPS28: Rating: AMBER; Mode of pathogenicity: None; Publications: 24942156; Phenotypes: Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3475 RPS29 Zornitza Stark Mode of inheritance for gene: RPS29 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3473 RPS29 Zornitza Stark reviewed gene: RPS29: Rating: AMBER; Mode of pathogenicity: None; Publications: 24829207; Phenotypes: Diamond-Blackfan anemia 13, MIM# 615909; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3473 UMOD Zornitza Stark Mode of inheritance for gene: UMOD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3472 UMOD Zornitza Stark edited their review of gene: UMOD: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3472 REN Zornitza Stark Phenotypes for gene: REN were changed from to Renal tubular dysgenesis, MIM# 267430; Autosomal dominant tubulointerstitial disease
Mendeliome v0.3470 REN Zornitza Stark Mode of inheritance for gene: REN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3469 REN Zornitza Stark reviewed gene: REN: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 31586593, 31406136, 28701203, 21473025; Phenotypes: Renal tubular dysgenesis, MIM# 267430, Autosomal dominant tubulointerstitial disease; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3465 UVSSA Zornitza Stark Mode of inheritance for gene: UVSSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3462 SEC23A Zornitza Stark Mode of inheritance for gene: SEC23A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3456 VPS33A Zornitza Stark Mode of inheritance for gene: VPS33A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3454 VPS33A Zornitza Stark reviewed gene: VPS33A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28013294, 27547915; Phenotypes: Mucopolysaccharidosis-plus syndrome (MIM#617303); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3452 COG2 Zornitza Stark Mode of inheritance for gene: COG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3450 COG2 Ain Roesley reviewed gene: COG2: Rating: RED; Mode of pathogenicity: None; Publications: 24784932; Phenotypes: Congenital disorder of glycosylation, type IIq (MIM# 617395); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3450 DACT1 Natalie Tan gene: DACT1 was added
gene: DACT1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: DACT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DACT1 were set to PMID: 28054444; 22610794; 19701191
Phenotypes for gene: DACT1 were set to ?Townes-Brocks syndrome 2 (OMIM #617466)
Review for gene: DACT1 was set to RED
Added comment: Webb et al. (2017) reported 6 affected members of a 3-generation family with ?Townes-Brocks syndrome-2, identified heterozygosity for a nonsense mutation in the DACT1 gene that segregated with disease. Clinical features include imperforate anus, rectovaginal fistula, crossed fused renal ectopia, vesicoureteral reflux, unilateral microtia, overfolded helices and cupped ears. One family member (proband's mother) with scoliosis and spina bifida occulta. Neural tube defects reported in a study of human fetuses (PMID: 22610794) and a mouse model (PMID: 19701191). Listed in Decipher v10.0 for an individual with abnormalities of (i) head or neck (ii) nervous system (iii) skeletal system. Unlike the gene SALL1 that causes Townes-Brocks syndrome 1, there is no information specifically relating to DACT1 with radial dysplasia, as these were not observed in the family with ?Townes-Brocks syndrome 2 (PMID: 28054444).
Sources: NHS GMS
Mendeliome v0.3450 G6PC3 Zornitza Stark Phenotypes for gene: G6PC3 were changed from to Dursun syndrome 612541; Neutropenia, severe congenital 4, autosomal recessive 612541
Mendeliome v0.3448 G6PC3 Zornitza Stark Mode of inheritance for gene: G6PC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3447 POGLUT1 Zornitza Stark Phenotypes for gene: POGLUT1 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696)
Mendeliome v0.3445 POGLUT1 Zornitza Stark Mode of inheritance for gene: POGLUT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3444 G6PC3 Belinda Chong reviewed gene: G6PC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21385794; Phenotypes: Dursun syndrome 612541, Neutropenia, severe congenital 4, autosomal recessive 612541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3444 POGLUT1 Ain Roesley reviewed gene: POGLUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27807076, 24387993; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 21 (MIM# 617232), Dowling-Degos disease 4 (MIM# 615696); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3444 SEC23A Paul De Fazio reviewed gene: SEC23A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3444 POFUT1 Ain Roesley reviewed gene: POFUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23684010, 29452367, 25157627; Phenotypes: Dowling-Degos disease 2 (MIM# 615327); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3442 ARSG Elena Savva reviewed gene: ARSG: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29300381, 20679209, 25452429, 26975023, 32455177; Phenotypes: Usher syndrome, type IV, MIM# 618144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3442 UVSSA Crystle Lee reviewed gene: UVSSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31421932; Phenotypes: UV-sensitive syndrome 3 (MIM#614640); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3440 FAM92A Zornitza Stark gene: FAM92A was added
gene: FAM92A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9, MIM# 618219
Review for gene: FAM92A was set to AMBER
Added comment: Single family and a mouse model reported.
Sources: Expert list
Mendeliome v0.3438 KIAA0825 Zornitza Stark gene: KIAA0825 was added
gene: KIAA0825 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0825 were set to 32147526; 30982135
Phenotypes for gene: KIAA0825 were set to Polydactyly, postaxial, type A10, MIM# 618498
Review for gene: KIAA0825 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Mendeliome v0.3435 ZNF141 Zornitza Stark Mode of inheritance for gene: ZNF141 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3433 ZNF141 Zornitza Stark reviewed gene: ZNF141: Rating: RED; Mode of pathogenicity: None; Publications: 23160277; Phenotypes: Polydactyly, postaxial, type A6, MIM# 615226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3428 NR0B1 Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3425 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3424 TFR2 Zornitza Stark Mode of inheritance for gene: TFR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3420 TFR2 Zornitza Stark Mode of inheritance for gene: TFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3417 ABCD3 Zornitza Stark Mode of inheritance for gene: ABCD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3413 NR0B1 Ain Roesley reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19508677, 26030781; Phenotypes: Adrenal hypoplasia, congenital (MIM# 300200); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3413 NSDHL Crystle Lee reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: 15689440; Phenotypes: CHILD syndrome (MMIM#308050); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3413 TFR2 Teresa Zhao reviewed gene: TFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24847265, 29743178; Phenotypes: Hemochromatosis, type 3 (MIM#604250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3412 ABCD3 Crystle Lee reviewed gene: ABCD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25168382; Phenotypes: ?Bile acid synthesis defect, congenital, 5 (MIM#616278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3410 NSMF Zornitza Stark Mode of inheritance for gene: NSMF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3408 NSMF Zornitza Stark reviewed gene: NSMF: Rating: RED; Mode of pathogenicity: None; Publications: 15362570, 17235395, 21700882; Phenotypes: Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3406 SPRY4 Zornitza Stark Mode of inheritance for gene: SPRY4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3404 SPRY4 Zornitza Stark reviewed gene: SPRY4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382; Phenotypes: Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3402 KISS1 Zornitza Stark Mode of inheritance for gene: KISS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3400 KISS1 Zornitza Stark reviewed gene: KISS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22335740, 25783047, 22766261, 17563351; Phenotypes: Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3398 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3396 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3394 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3392 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: AMBER; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3392 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Mendeliome v0.3389 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3387 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3385 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3384 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3381 CUX2 Zornitza Stark Mode of inheritance for gene: CUX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3378 DPM1 Zornitza Stark Mode of inheritance for gene: DPM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3377 CUX2 Elena Savva reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 2963073, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, 618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3377 DPM1 Elena Savva reviewed gene: DPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23856421; Phenotypes: Congenital disorder of glycosylation, type Ie, 608799; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3376 GIPC1 Zornitza Stark gene: GIPC1 was added
gene: GIPC1 was added to Mendeliome. Sources: Literature
5'UTR, STR tags were added to gene: GIPC1.
Mode of inheritance for gene: GIPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIPC1 were set to 32413282
Phenotypes for gene: GIPC1 were set to Oculopharyngodistal myopathy-2 (OPDM2), MIM#618940
Review for gene: GIPC1 was set to AMBER
Added comment: 19 families reported with heterozygous trinucleotide repeat expansion in the 5-prime untranslated region and onset of distal muscle weakness, mainly of the lower limbs, and/or ophthalmoplegia in the second or third decades of life. Note this is unlikely to be tractable currently by most NGS assays.
Sources: Literature
Mendeliome v0.3373 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3369 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3368 SMC3 Elena Savva reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18996922, 25655089, 31334757; Phenotypes: ornelia de Lange syndrome 3, 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3368 DEAF1 Elena Savva reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 30923367, PMID 24726472; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3368 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3367 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Mendeliome v0.3364 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3363 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31575858, 22610116, 22608503; Phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, mild ID, similar facies, myopathy, cerebral white matter hyperintensities, cardiac systolic dysfunction; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3361 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3359 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3357 PIGM Zornitza Stark Mode of inheritance for gene: PIGM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3353 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3350 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3347 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3343 ESR2 Zornitza Stark Mode of inheritance for gene: ESR2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29261182, 9861029, 30113650; Phenotypes: 46,XY disorder of sex development, Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3342 PIGM Paul De Fazio reviewed gene: PIGM: Rating: AMBER; Mode of pathogenicity: None; Publications: 31445883, 16767100; Phenotypes: portal vein thrombosis, persistent absence seizures, macrocephaly, infantile-onset cerebrovascular thrombotic events; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3342 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3340 DMRT1 Zornitza Stark Mode of inheritance for gene: DMRT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3338 DMRT1 Zornitza Stark reviewed gene: DMRT1: Rating: RED; Mode of pathogenicity: None; Publications: 31479588, 24934491, 29527098; Phenotypes: Azoospermia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3336 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3334 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: 19361780, 31719618, 23219007; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3334 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3331 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Compound heterozgyous variants reported in one patient. Insufficient evidence supporting gene disease association
Sources: Expert Review
Mendeliome v0.3329 CNPY3 Zornitza Stark Mode of inheritance for gene: CNPY3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3328 CNPY3 Zornitza Stark reviewed gene: CNPY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29394991, 30237576; Phenotypes: Epileptic encephalopathy, early infantile, 60 (MIM 617929); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3327 KIF21B Zornitza Stark gene: KIF21B was added
gene: KIF21B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Mode of pathogenicity for gene: KIF21B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Expert Review
Mendeliome v0.3325 TBC1D2B Zornitza Stark gene: TBC1D2B was added
gene: TBC1D2B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.
Sources: Expert Review
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Mendeliome v0.3321 CCDC174 Zornitza Stark gene: CCDC174 was added
gene: CCDC174 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816). Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype. Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Expert Review
Mendeliome v0.3318 ABCA2 Zornitza Stark gene: ABCA2 was added
gene: ABCA2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Expert Review
Mendeliome v0.3317 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Mendeliome v0.3315 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3314 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3310 TTI1 Zornitza Stark Mode of inheritance for gene: TTI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3308 SGMS2 Bryony Thompson gene: SGMS2 was added
gene: SGMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 30779713; 32028018
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia MIM#126550
Review for gene: SGMS2 was set to GREEN
Added comment: 12 patients from 6 unrelated families with the same stopgain variant (p.Arg50*), with osteoporosis that resembles osteogenesis imperfecta. In vitro over-expression assays of the variant demonstrate protein that was completely mislocalized in the cytosolic and nuclear compartments. 2 unrelated families were heterozygous for 2 missense (p.Ile62Ser, p.Met64Arg) with bone fragility and severe short stature, and spondylometaphyseal dysplasia. In vitro assays of each variant demonstrated an enhanced rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum.
Sources: Expert list
Mendeliome v0.3305 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3303 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3301 PIP5K1C Zornitza Stark Mode of inheritance for gene: PIP5K1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3299 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701898; Phenotypes: Lethal congenital contractural syndrome 3, MIM# 611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3297 ERBB3 Zornitza Stark Mode of inheritance for gene: ERBB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3295 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 17701904, 31752936; Phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3293 DPM2 Zornitza Stark Mode of inheritance for gene: DPM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3291 DPM2 Zornitza Stark reviewed gene: DPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23109149; Phenotypes: Congenital disorder of glycosylation, type Iu, MIM# 615042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3291 C17orf62 Zornitza Stark Phenotypes for gene: C17orf62 were changed from Chronic granulomatous disease to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 C17orf62 Zornitza Stark edited their review of gene: C17orf62: Changed phenotypes: Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Mendeliome v0.3290 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Mendeliome v0.3288 DYSF Zornitza Stark Mode of inheritance for gene: DYSF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3287 NEB Zornitza Stark Phenotypes for gene: NEB were changed from to Nemaline myopathy 2, autosomal recessive 256030
Mendeliome v0.3285 NEB Zornitza Stark Mode of inheritance for gene: NEB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3284 MRPS34 Zornitza Stark reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, MIM# 617664; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3282 MRPS34 Zornitza Stark Mode of inheritance for gene: MRPS34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 MRPS34 Elena Savva reviewed gene: MRPS34: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28777931; Phenotypes: Combined oxidative phosphorylation deficiency 32, 61766; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 NEB Elena Savva reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25205138; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3281 DYSF Elena Savva reviewed gene: DYSF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27602406; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3279 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3278 GLS Zornitza Stark edited their review of gene: GLS: Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412, Catarct; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3278 PYCR1 Dean Phelan changed review comment from: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.; to: Aortopathy/Connective tissue review

Variants in this gene are associated with Cutis Laxa:
Cutis laxa type 2 (ARCL2, [MIM 219200]) is an autosomal-recessive multisystem disorder with prominent connective-tissue features characterized by the appearance of premature aging, particularly wrinkled and lax skin with reduced elasticity.

GEL PanelApp: Green in EDS panel - clinical features overlapping EDS
Cutis laxa, autosomal recessive, type IIIB (ARCL3B) PMID: 19648921,4076251, 22052856
Cutis laxa, autosomal recessive, type IIB (ARCL2B) PMID: 19576563, 19648921, 9648921, 22052856, 28294978 AR

PMID: 27756598: a homozygous mutation in PYCR1 segregating in the family with the affected individuals with complex connective tissue disorder and severe intellectual disability.
Mendeliome v0.3276 PYCR1 Seb Lunke Mode of inheritance for gene: PYCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3273 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3271 MTMR14 Zornitza Stark Added comment: Comment when marking as ready: Single family and animal models; postulated to be a modifier in the other family.
Mendeliome v0.3269 MTMR14 Zornitza Stark Mode of inheritance for gene: MTMR14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3268 P4HA1 Zornitza Stark gene: P4HA1 was added
gene: P4HA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: P4HA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HA1 were set to 28419360
Phenotypes for gene: P4HA1 were set to Joint hypermobility; Contractures; Hypotonia; Mild skeletal dysplasia without bone fragility; High myopia
Review for gene: P4HA1 was set to RED
Added comment: Single family reported with two affected individuals.
Sources: Expert list
Mendeliome v0.3267 ROBO3 Ain Roesley reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15105459, 32373565; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 PIGY Elena Savva reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3267 PYCR1 Dean Phelan reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19648921, 4076251, 22052856, 19576563, 19648921, 9648921, 22052856, 28294978, 27756598; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3266 GGPS1 Zornitza Stark gene: GGPS1 was added
gene: GGPS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency
Review for gene: GGPS1 was set to GREEN
Added comment: 11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature
Mendeliome v0.3265 MTMR14 Elena Savva reviewed gene: MTMR14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20400459, 20817957, 19465920, 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of}, MIM# 160150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3264 DNMBP Seb Lunke gene: DNMBP was added
gene: DNMBP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNMBP were set to 30290152
Phenotypes for gene: DNMBP were set to congenital cataract
Review for gene: DNMBP was set to GREEN
gene: DNMBP was marked as current diagnostic
Added comment: Multiple individuals from three independent large consanguineous families with bilateral infantile cataracts. Seperate hom nonsense variants.
Sources: Literature
Mendeliome v0.3263 CRYGA Zornitza Stark gene: CRYGA was added
gene: CRYGA was added to Mendeliome. Sources: Expert list
refuted tags were added to gene: CRYGA.
Mode of inheritance for gene: CRYGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CRYGA were set to 30450742; 28839118
Phenotypes for gene: CRYGA were set to Cataract
Review for gene: CRYGA was set to RED
Added comment: Reported as potentially disease causing in multiple individuals from two seperate families, but in both cases variant is present in the general population (20 Hets for one variant, >1000 hets and 9 homs in other variant)
Sources: Expert list
Mendeliome v0.3262 AKR1E2 Zornitza Stark gene: AKR1E2 was added
gene: AKR1E2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AKR1E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1E2 were set to 26622071
Phenotypes for gene: AKR1E2 were set to congenital cataracts
Review for gene: AKR1E2 was set to RED
Added comment: Same family with homozygous canonical splice variants and 3 cases of congenital cataract described in 2012 (original) and 2015 (review). No other descriptions since.
Sources: Expert list
Mendeliome v0.3261 ADAMTSL4 Zornitza Stark Phenotypes for gene: ADAMTSL4 were changed from to Ectopia lentis, isolated, autosomal recessive, MIM# 225100
Mendeliome v0.3259 ADAMTSL4 Zornitza Stark Mode of inheritance for gene: ADAMTSL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3258 ADAMTSL4 Zornitza Stark reviewed gene: ADAMTSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19200529, 20564469, 20141359, 21051722; Phenotypes: Ectopia lentis, isolated, autosomal recessive, MIM# 225100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3256 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3255 HIST1H4C Zornitza Stark reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: 28920961; Phenotypes: Growth delay, microcephaly and intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3253 SFTPA1 Zornitza Stark Mode of inheritance for gene: SFTPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3251 SFTPA1 Zornitza Stark reviewed gene: SFTPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31601679, 30854216, 28869238, 26792177; Phenotypes: Idiopathic pulmonary fibrosis; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Mendeliome v0.3248 ASPRV1 Ee Ming Wong gene: ASPRV1 was added
gene: ASPRV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASPRV1 were set to PMID: 32516568
Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis
Review for gene: ASPRV1 was set to GREEN
gene: ASPRV1 was marked as current diagnostic
Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds
-mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing
Sources: Literature
Mendeliome v0.3244 LGR4 Zornitza Stark Mode of inheritance for gene: LGR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3242 SREBF1 Paul De Fazio gene: SREBF1 was added
gene: SREBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
gene: SREBF1 was marked as current diagnostic
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Mendeliome v0.3242 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3241 BTG4 Ain Roesley gene: BTG4 was added
gene: BTG4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BTG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTG4 were set to PMID: 32502391
Phenotypes for gene: BTG4 were set to Zygotic cleavage failure (ZCF)
Penetrance for gene: BTG4 were set to unknown
Added comment: PMID: 32502391
- 4 affecteds from 4 families including 3 consanguineous families. 3 PTVs + 1 splice.
- in vitro assays in HELA cells showed all PTVs had complete loss of protein. The missense variant had abolished interaction with CNOT7
- In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF
Sources: Literature
Mendeliome v0.3240 KIAA1217 Zornitza Stark gene: KIAA1217 was added
gene: KIAA1217 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA1217 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIAA1217 were set to 32369272
Phenotypes for gene: KIAA1217 were set to Vertebral anomalies, syndromic and non-syndromic
Review for gene: KIAA1217 was set to AMBER
Added comment: 10 families reported, however note only 3 of the variants were absent from gnomad, inheritance not reported, most variants are missense.
Sources: Literature
Mendeliome v0.3239 TRIP13 Ain Roesley reviewed gene: TRIP13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32473092; Phenotypes: female infertility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3239 LGR4 Elena Savva reviewed gene: LGR4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32493844; Phenotypes: {Bone mineral density, low, susceptibility to} 615311; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3239 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Mendeliome v0.3236 HOXD10 Zornitza Stark Mode of inheritance for gene: HOXD10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3234 HOXD10 Crystle Lee reviewed gene: HOXD10: Rating: AMBER; Mode of pathogenicity: None; Publications: 15146389, 16450407; Phenotypes: Charcot-Marie-Tooth disease, foot deformity of, Vertical talus, congenital (MIM#192950); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3232 ADPRHL2 Zornitza Stark Mode of inheritance for gene: ADPRHL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3231 ADPRHL2 Zornitza Stark changed review comment from: Ataxia is part of the phenotype.
Sources: Expert list; to: 14 families reported, onset is in the first years of life following normal early development. Patients have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.
Sources: Expert list
Mendeliome v0.3230 GPR161 Zornitza Stark gene: GPR161 was added
gene: GPR161 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to 31609649
Phenotypes for gene: GPR161 were set to Predisposition to paediatric medulloblastoma
Review for gene: GPR161 was set to GREEN
Added comment: 6 unrelated individuals reported with germline variants, 5 with truncating, one missense. Somatic second hit in tumour tissue.
Sources: Literature
Mendeliome v0.3227 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3226 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566, 29322246, 31440728, 31685013; Phenotypes: Epilepsy with myoclonic absences, intellectual disability, SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3225 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Mendeliome v0.3222 MRAS Zornitza Stark gene: MRAS was added
gene: MRAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were set to Noonan syndrome
Review for gene: MRAS was set to AMBER
Added comment: Two unrelated individuals reported with de novo variants in this gene. Rated as LIMITED by ClinGen.
Sources: Expert list
Mendeliome v0.3219 A2ML1 Zornitza Stark Mode of inheritance for gene: A2ML1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3217 A2ML1 Zornitza Stark reviewed gene: A2ML1: Rating: RED; Mode of pathogenicity: None; Publications: 24939586, 25862627; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3216 NRG1 Bryony Thompson gene: NRG1 was added
gene: NRG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NRG1 were set to 22574178; 21706185; 28190554
Phenotypes for gene: NRG1 were set to Hirschsprung disease
Review for gene: NRG1 was set to AMBER
Added comment: Has been reported as a Hirschsprung disease susceptibility loci, with common, low-penetrance polymorphisms that contribute only partially to risk and can act as genetic modifiers. There are also two publications with rare variants reported in this gene (at least one de novo) and supporting in vitro functional assays. A null zebrafish model was also supportive of a role in Hirschsprung disease.
Sources: Expert list
Mendeliome v0.3213 FLRT3 Zornitza Stark Mode of inheritance for gene: FLRT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3211 FLRT3 Zornitza Stark reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3211 CCDC32 Zornitza Stark Added comment: Comment when marking as ready: Three affected individuals from two unrelated families, supportive animal model and other functional data consistent with this being a ciliopathy.
Mendeliome v0.3203 RAD21 Zornitza Stark Mode of inheritance for gene: RAD21 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3202 CAPZA2 Eleanor Williams gene: CAPZA2 was added
gene: CAPZA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Mendeliome v0.3202 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PPP3R1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: PLEK was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Mendeliome v0.3202 RAD21 Sarah Leigh reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 31334757, 31704779; Phenotypes: Cornelia de Lange syndrome 4 614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3202 CCDC32 Eleanor Williams gene: CCDC32 was added
gene: CCDC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC32 were set to 32307552
Phenotypes for gene: CCDC32 were set to craniofacial, cardiac and neurodevelopmental anomalies
Review for gene: CCDC32 was set to AMBER
Added comment: PMID: 32307552 - Harel et al 2020 - reports 2 unrelated consanguineous families with probands with homozygous frameshift variants in CCDC32. Parents are heterozygous. Phenotype is a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies. Functional studies in zebrafish show that ccdc32 depletion impairs cilia formation and shows a role for ccdc32 in craniofacial, brain and left/right axis development.
Sources: Literature
Mendeliome v0.3202 SKIV2L Zornitza Stark reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichohepatoenteric syndrome 2, MIM# 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3200 SKIV2L Zornitza Stark Mode of inheritance for gene: SKIV2L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3198 NLRP5 Zornitza Stark gene: NLRP5 was added
gene: NLRP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NLRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLRP5 were set to 32222962; 31829238; 30877238
Phenotypes for gene: NLRP5 were set to Early embryonic arrest
Review for gene: NLRP5 was set to AMBER
Added comment: At least two families reported.
Sources: Literature
Mendeliome v0.3196 EXOC7 Zornitza Stark gene: EXOC7 was added
gene: EXOC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Mendeliome v0.3195 HNRNPH1 Zornitza Stark gene: HNRNPH1 was added
gene: HNRNPH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant. 2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Mendeliome v0.3194 PDCD6IP Zornitza Stark gene: PDCD6IP was added
gene: PDCD6IP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to 32286682
Phenotypes for gene: PDCD6IP were set to Microcephaly; intellectual disability
Review for gene: PDCD6IP was set to AMBER
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Mendeliome v0.3192 NME5 Zornitza Stark gene: NME5 was added
gene: NME5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NME5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME5 were set to 32185794
Phenotypes for gene: NME5 were set to Primary ciliary dyskinesia
Review for gene: NME5 was set to AMBER
Added comment: One patient with PCD with situs solitus, with radial spokes (RS) and central pair (CP) defects. Patient had a homozygous nonsense variant in NME5, with parents as carriers. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.
Sources: Literature
Mendeliome v0.3189 ADAMTS19 Zornitza Stark reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32323311, 31844321; Phenotypes: Heart valve disease (HVD); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3189 EMILIN1 Naomi Baker gene: EMILIN1 was added
gene: EMILIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Phenotypes for gene: EMILIN1 were set to peripheral neuropathy
Penetrance for gene: EMILIN1 were set to unknown
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Mendeliome v0.3188 ADAMTS3 Zornitza Stark gene: ADAMTS3 was added
gene: ADAMTS3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ADAMTS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS3 were set to 28985353; 30450763
Phenotypes for gene: ADAMTS3 were set to Hennekam lymphangiectasia-lymphedema syndrome 3 (618154)
Review for gene: ADAMTS3 was set to GREEN
Added comment: Two families reported, supportive functional data.
Sources: Expert list
Mendeliome v0.3185 TBX5 Zornitza Stark edited their review of gene: TBX5: Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3185 MCM3AP Eleanor Williams reviewed gene: MCM3AP: Rating: ; Mode of pathogenicity: None; Publications: 32202298; Phenotypes: peripheral neuropathy with or without impaired intellectual development MIM#618124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3185 SP6 Eleanor Williams gene: SP6 was added
gene: SP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574
Phenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta
Review for gene: SP6 was set to AMBER
Added comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 )
Sources: Literature
Mendeliome v0.3183 MYH8 Zornitza Stark Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3182 MYH8 Teresa Zhao reviewed gene: MYH8: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28377322, 18049072, 17041932; Phenotypes: Trismus-pseudocamptodactyly syndrome MIM# 158300, Carney complex variant MIM# 608837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3182 CACNB1 Zornitza Stark gene: CACNB1 was added
gene: CACNB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNB1 were set to 27832566; 8943043; 29212769
Phenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility
Added comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition).
Sources: Expert list
Mendeliome v0.3178 GATA6 Zornitza Stark Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3177 GATA6 Elena Savva reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:20581743, 19666519; Phenotypes: Pancreatic agenesis and congenital heart defects, 600001, Atrial septal defect 9, 614475, Atrioventricular septal defect 5, 614474, Tetralogy of Fallot, 187500, Persistent truncus arteriosus, 217095; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.3177 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3176 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Mendeliome v0.3176 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from Intellectual disability; autism; Rett-like features; epileptic encephalopathy to Intellectual disability; autism; Rett-like features; epileptic encephalopathy; Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3175 GRIA2 Zornitza Stark edited their review of gene: GRIA2: Changed phenotypes: Intellectual disability, autism, Rett-like features, epileptic encephalopathy, Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Mendeliome v0.3174 TSHZ1 Zornitza Stark changed review comment from: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487).; to: Two individuals reported with LoF variants, both with a phenotype of congenital aural atresia and hyposmia (PMID: 22152683). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). Tsh2 null mouse model showed a middle ear malformation, and neonatal lethality. A conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (PMIDs: 24487590; 17586487). Also note original report contains four individuals with deletions of this gene, further supporting gene-disease association.
Mendeliome v0.3174 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3171 TSHZ1 Zornitza Stark Mode of inheritance for gene: TSHZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 TSHZ1 Zornitza Stark reviewed gene: TSHZ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15834955, 22152683, 17586487, 24487590; Phenotypes: Aural atresia, congenital, MIM# 607842, Hyposmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3170 ZBTB18 Zornitza Stark Phenotypes for gene: ZBTB18 were changed from to Mental retardation, autosomal dominant 22, MIM# 612337
Mendeliome v0.3167 ZBTB18 Zornitza Stark Mode of inheritance for gene: ZBTB18 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3165 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ESR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3164 ZBTB18 Elena Savva reviewed gene: ZBTB18: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 27598823, 29573576; Phenotypes: Mental retardation, autosomal dominant 22 612337; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3163 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3161 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3158 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3157 UBE2A Zornitza Stark reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3157 SETD2 Michelle Torres reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, 616831 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3156 AXL Bryony Thompson gene: AXL was added
gene: AXL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 18787040; 24476074
Phenotypes for gene: AXL were set to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism
Review for gene: AXL was set to AMBER
Added comment: Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.
Sources: Literature
Mendeliome v0.3153 GANAB Zornitza Stark Mode of inheritance for gene: GANAB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3152 GANAB Zornitza Stark reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259053; Phenotypes: Polycystic kidney disease 3, MIM# 600666; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3150 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Nueromuscular disorder
Review for gene: GOLGA2 was set to GREEN
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients + animal model
Sources: Expert list
Mendeliome v0.3149 MUC7 Bryony Thompson reviewed gene: MUC7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Asthma, protection against} MIM#600807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3145 PHOX2A Zornitza Stark Mode of inheritance for gene: PHOX2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3143 PHOX2A Elena Savva reviewed gene: PHOX2A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11600883, 18323871; Phenotypes: Fibrosis of extraocular muscles, congenital, 2 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3142 ABCC1 Zornitza Stark Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss to Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3141 ABCC1 Zornitza Stark edited their review of gene: ABCC1: Changed phenotypes: Deafness-77, autosomal dominant (DFNA77), MIM#618915
Mendeliome v0.3138 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3136 ANKRD1 Zornitza Stark reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: 19608030, 19525294, 30681346; Phenotypes: Hypertrophic cardiomyopathy, Dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3134 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3132 CALR3 Zornitza Stark reviewed gene: CALR3: Rating: RED; Mode of pathogenicity: None; Publications: 29988065; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3130 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3129 ALPK3 Zornitza Stark reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26846950, 27106955, 32480058; Phenotypes: Cardiomyopathy, familial hypertrophic 27, MIM# 618052; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3127 HSF4 Zornitza Stark Mode of inheritance for gene: HSF4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3126 HSF4 Zornitza Stark reviewed gene: HSF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31815953, 29243736, 26490182; Phenotypes: Cataract 5, multiple types, 116800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3125 FITM2 Bryony Thompson gene: FITM2 was added
gene: FITM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Mendeliome v0.3121 CHD1L Zornitza Stark Mode of inheritance for gene: CHD1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3119 CHD1L Zornitza Stark reviewed gene: CHD1L: Rating: RED; Mode of pathogenicity: None; Publications: 22146311, 24429398; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3117 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3116 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from to Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443
Mendeliome v0.3115 MEF2C Zornitza Stark Mode of inheritance for gene: MEF2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3112 KDM6A Zornitza Stark Mode of inheritance for gene: KDM6A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3111 KDM6A Elena Savva reviewed gene: KDM6A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27302555, 24664873; Phenotypes: Kabuki syndrome 2, 300867; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.3111 MEF2C Elena Savva reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chromosome 5q14.3 deletion syndrome, 613443, Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3111 NEXMIF Elena Savva reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.3110 STAG3 Bryony Thompson gene: STAG3 was added
gene: STAG3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: STAG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAG3 were set to 24597867; 26059840; 31803224; 31363903
Phenotypes for gene: STAG3 were set to Premature ovarian failure 8 MIM#615723
Review for gene: STAG3 was set to GREEN
Added comment: At least four unrelated families with ovarian failure and a supporting null mouse model.
Sources: Expert list
Mendeliome v0.3108 SOHLH1 Bryony Thompson gene: SOHLH1 was added
gene: SOHLH1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SOHLH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SOHLH1 were set to 25774885; 16690745; 31042289; 20506135; 28718531
Phenotypes for gene: SOHLH1 were set to Ovarian dysgenesis 5 MIM#617690; Spermatogenic failure 32 MIM#618115
Review for gene: SOHLH1 was set to GREEN
Added comment: Women in 3 unrelated families with ovarian dysgenesis and homozygous variants, and a supporting null mouse model.
At least 4 males with heterozygous variants and spermatogenic failure.
Sources: Expert list
Mendeliome v0.3106 HFM1 Bryony Thompson gene: HFM1 was added
gene: HFM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HFM1 were set to 23555294; 24597873; 31279343
Phenotypes for gene: HFM1 were set to Premature ovarian failure 9 MIM#615724
Review for gene: HFM1 was set to GREEN
Added comment: Three cases from 2 unrelated families with compound heterozygous variants, and a single family with a heterozygous variant have been reported with ovarian failure. There is also a supporting null mouse model.
Sources: Expert list
Mendeliome v0.3103 NEK9 Zornitza Stark Mode of inheritance for gene: NEK9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3101 NEK9 Zornitza Stark reviewed gene: NEK9: Rating: RED; Mode of pathogenicity: None; Publications: 26908619; Phenotypes: Lethal congenital contracture syndrome 10, MIM# 617022, Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3099 MSTN Zornitza Stark Mode of inheritance for gene: MSTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3097 MSTN Zornitza Stark reviewed gene: MSTN: Rating: RED; Mode of pathogenicity: None; Publications: 15215484; Phenotypes: Muscle hypertrophy, MIM# 614160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3095 HSPB8 Zornitza Stark Mode of inheritance for gene: HSPB8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3092 AMPD1 Zornitza Stark Mode of inheritance for gene: AMPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3090 AMPD1 Zornitza Stark reviewed gene: AMPD1: Rating: RED; Mode of pathogenicity: None; Publications: 21343608, 27296017; Phenotypes: Myopathy due to myoadenylate deaminase deficiency (MIM#615511); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3090 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Mendeliome v0.3089 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3088 DCAF8 Bryony Thompson gene: DCAF8 was added
gene: DCAF8 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCAF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCAF8 were set to 24500646
Phenotypes for gene: DCAF8 were set to Giant axonal neuropathy 2, autosomal dominant MIM#610100
Review for gene: DCAF8 was set to AMBER
Added comment: A single large family segregating a missense variant and in vitro functional assays demonstrating the variant reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function
Sources: Expert list
Mendeliome v0.3086 ARL6IP1 Bryony Thompson gene: ARL6IP1 was added
gene: ARL6IP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL6IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARL6IP1 were set to 24482476; 31272422; 30980493; 28471035
Phenotypes for gene: ARL6IP1 were set to Spastic paraplegia 61, autosomal recessive MIM#615685
Review for gene: ARL6IP1 was set to GREEN
gene: ARL6IP1 was marked as current diagnostic
Added comment: At least 4 families reported with paediatric onset complicated spastic paraplegia and neuropathy. Supporting zebrafish model.
Sources: Expert list
Mendeliome v0.3084 PMP2 Bryony Thompson gene: PMP2 was added
gene: PMP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMP2 were set to 26257172; 26828946; 27009151
Phenotypes for gene: PMP2 were set to Charcot-Marie-Tooth disease, demyelinating, type 1G MIM#618279
Review for gene: PMP2 was set to GREEN
Added comment: 4 unrelated families reported with missense variants, with supporting transgenic mouse and null zebrafish models.
Sources: Expert list
Mendeliome v0.3082 HPRT1 Zornitza Stark Mode of inheritance for gene: HPRT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3081 HPRT1 Ain Roesley reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20176575; Phenotypes: HPRT-related gout (MIM# 300323), Lesch-Nyhan syndrome (MIM# 300322); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.3079 ASTN2 Zornitza Stark Mode of inheritance for gene: ASTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3078 SI Zornitza Stark Phenotypes for gene: SI were changed from to Sucrase-isomaltase deficiency, congenital #222900
Mendeliome v0.3076 SI Zornitza Stark Mode of inheritance for gene: SI was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3074 ADGRG1 Elena Savva reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24531968; Phenotypes: Polymicrogyria, bilateral frontoparietal 606854, Polymicrogyria, bilateral perisylvian 615752; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3074 SI Elena Savva reviewed gene: SI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3149304, 31557950; Phenotypes: Sucrase-isomaltase deficiency, congenital #222900; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3073 RYR3 Zornitza Stark gene: RYR3 was added
gene: RYR3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RYR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RYR3 were set to 29498452; 32451403; 31230720
Phenotypes for gene: RYR3 were set to Nemaline myopathy; fetal akinesia; arthrogryposis
Review for gene: RYR3 was set to AMBER
Added comment: One family reported with nemaline myopathy and other cases reported as part of large fetal akinesia/arthrogryposis discovery cohorts reporting multiple novel gene candidates.
Sources: Expert list
Mendeliome v0.3072 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Mendeliome v0.3069 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3068 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3063 PLAG1 Zornitza Stark Mode of inheritance for gene: PLAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3061 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28796236, 29913240; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3058 NEFH Zornitza Stark Mode of inheritance for gene: NEFH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3055 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3052 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3051 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973, 29654216; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718, Fanconi renotubular syndrome 1, MIM# 134600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3051 TRIM69 Zornitza Stark gene: TRIM69 was added
gene: TRIM69 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRIM69 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TRIM69 were set to 22105173
Phenotypes for gene: TRIM69 were set to Susceptibility to herpes simplex encephalitis
Review for gene: TRIM69 was set to RED
Added comment: One individual with bi-allelic and one individual with mono-allelic variants in this gene described.
Sources: Expert list
Mendeliome v0.3050 SLC6A1 Chern Lim reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3050 NEFH Chern Lim reviewed gene: NEFH: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30992180, 27040688, 28709447; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2CC, MIM#616924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.3050 LIMS2 Zornitza Stark gene: LIMS2 was added
gene: LIMS2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIMS2 were set to 25589244; 16317048
Phenotypes for gene: LIMS2 were set to Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue MIM#616827
Review for gene: LIMS2 was set to RED
Added comment: Only one family reported and Pinch2 -/- mice were viable and fertile with no apparent phenotype.
Sources: Expert list
Mendeliome v0.3049 FAN1 Elena Savva reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22772369; Phenotypes: Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3049 RAD21 Elena Savva reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31334757, 25575569, 32193685; Phenotypes: ?Mungan syndrome, 611376, Cornelia de Lange syndrome 4, 614701, Holoprocencephaly; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.3048 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Mendeliome v0.3045 SLC12A6 Zornitza Stark Mode of inheritance for gene: SLC12A6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3044 SLC12A6 Zornitza Stark reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31439721; Phenotypes: Andermann syndrome, Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum, Intermediate CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3042 EWSR1 Seb Lunke Mode of inheritance for gene: EWSR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3040 EWSR1 Seb Lunke reviewed gene: EWSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29731676, 22454397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3037 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Mendeliome v0.3033 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3032 RHOBTB2 Elena Savva reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:29276004, 29768694; Phenotypes: Epileptic encephalopathy, early infantile, 64, 618004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.3030 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3029 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3028 NUP88 Zornitza Stark gene: NUP88 was added
gene: NUP88 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP88 were set to 30543681
Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393
Review for gene: NUP88 was set to GREEN
Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model.
Sources: Literature
Mendeliome v0.3025 SMO Zornitza Stark Mode of inheritance for gene: SMO was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 SMO Zornitza Stark reviewed gene: SMO: Rating: GREEN; Mode of pathogenicity: None; Publications: 32413283, 27236920; Phenotypes: Microcephaly, congenital heart disease, polydactyly, aganglionosis, Curry-Jones syndrome, somatic mosaic 601707; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3024 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Mendeliome v0.3022 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Mendeliome v0.3021 PYGM Zornitza Stark Phenotypes for gene: PYGM were changed from to McArdle disease, MIM# 232600; Glycogen storage disease, autosomal dominant
Mendeliome v0.3019 PYGM Zornitza Stark Mode of inheritance for gene: PYGM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3018 PYGM Zornitza Stark reviewed gene: PYGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32386344; Phenotypes: McArdle disease, MIM# 232600, Glycogen storage disease, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.3017 PERP Zornitza Stark gene: PERP was added
gene: PERP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PERP were set to 31898316
Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet
Review for gene: PERP was set to AMBER
Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible.
Sources: Literature
Mendeliome v0.3015 ADCY6 Zornitza Stark gene: ADCY6 was added
gene: ADCY6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADCY6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058
Phenotypes for gene: ADCY6 were set to Lethal congenital contracture syndrome 8, OMIM # 616287
Review for gene: ADCY6 was set to GREEN
Added comment: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Mendeliome v0.3014 DSCR3 Zornitza Stark gene: DSCR3 was added
gene: DSCR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DSCR3 were set to 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Mendeliome v0.3013 LEF1 Zornitza Stark gene: LEF1 was added
gene: LEF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEF1 were set to 32022899
Phenotypes for gene: LEF1 were set to Ectodermal dysplasia, no OMIM# yet
Review for gene: LEF1 was set to RED
Added comment: In mice, targeted inactivation of the LEF1 gene results in a complete block of development of multiple ectodermal appendages. One report of two unrelated patients with 4q25 de novo deletion encompassing LEF1 , associated with severe oligodontia of primary and permanent dentition, hypotrichosis and hypohidrosis compatible with hypohidrotic ectodermal dysplasia. So far, no pathogenic variants or variations involving the LEF1 gene have been reported in human.
Sources: Literature
Mendeliome v0.3010 OTUD7A Zornitza Stark gene: OTUD7A was added
gene: OTUD7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Mendeliome v0.3009 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Mendeliome v0.3007 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3006 GATAD2B Zornitza Stark reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3003 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3002 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949313; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3000 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2999 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2997 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2994 DNAL1 Zornitza Stark Mode of inheritance for gene: DNAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2992 DNAL1 Zornitza Stark reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: Ciliary dyskinesia, primary, 16, MIM# 614017; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2990 DNAH8 Zornitza Stark Mode of inheritance for gene: DNAH8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2988 DNAH8 Zornitza Stark reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: None; Publications: 31178125, 24307375; Phenotypes: Asthenozoospermia, primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2987 TTC5 Zornitza Stark gene: TTC5 was added
gene: TTC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Review for gene: TTC5 was set to GREEN
Added comment: Eleven individuals from seven families reported.
Sources: Literature
Mendeliome v0.2982 DRC1 Zornitza Stark Mode of inheritance for gene: DRC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2981 DRC1 Zornitza Stark edited their review of gene: DRC1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2979 TLL1 Zornitza Stark Mode of inheritance for gene: TLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2978 TLL1 Dean Phelan reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18830233, 30538173, 27418595, 31570783; Phenotypes: Atrial septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2977 HIST1H4J Zornitza Stark gene: HIST1H4J was added
gene: HIST1H4J was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Review for gene: HIST1H4J was set to AMBER
Added comment: Single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Mendeliome v0.2974 MCIDAS Zornitza Stark Mode of inheritance for gene: MCIDAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 MCIDAS Zornitza Stark reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25048963; Phenotypes: Ciliary dyskinesia, primary, 42 (MIM#618695); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2973 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness; Contractures
Mendeliome v0.2972 TOR1AIP1 Zornitza Stark Phenotypes for gene: TOR1AIP1 were changed from Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072 to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072; Progeroid appearance; Cataracts; Microcephaly; Deafness
Mendeliome v0.2968 EFEMP1 Zornitza Stark Mode of inheritance for gene: EFEMP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2966 ZFYVE27 Bryony Thompson reviewed gene: ZFYVE27: Rating: RED; Mode of pathogenicity: None; Publications: 16826525, 29980238, 18606302; Phenotypes: Spastic paraplegia 33, autosomal dominant MIM#610244; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2966 EFEMP1 Zornitza Stark reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32006683, 31792352; Phenotypes: Doyne honeycomb degeneration of retina, MIM# 126600, EFEMP1-related connective tissue disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2966 TOR1AIP1 Kristin Rigbye reviewed gene: TOR1AIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32055997; Phenotypes: TOR1AIP1-associated nuclear envelopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2965 USP8 Bryony Thompson gene: USP8 was added
gene: USP8 was added to Mendeliome. Sources: Expert list
somatic tags were added to gene: USP8.
Mode of inheritance for gene: USP8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: USP8 were set to 25675982; 24482476; 25485838; 25942478
Phenotypes for gene: USP8 were set to Pituitary adenoma 4, ACTH-secreting, somatic MIM#219090; hereditary spastic paraplegia
Review for gene: USP8 was set to GREEN
Added comment: Recurrent somatic gain of function missense variants in pituitary adenomas cause Cushing's disease.
A single family reported with spastic paraplegia with a homozygous variant, and a zebrafish model with a movement disorder.
Sources: Expert list
Mendeliome v0.2959 SCYL2 Zornitza Stark gene: SCYL2 was added
gene: SCYL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 31960134; 26203146
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome
Review for gene: SCYL2 was set to AMBER
Added comment: Two unrelated families reported with AMC, variable other features including microcephaly.
Sources: Literature
Mendeliome v0.2955 VWA3B Bryony Thompson gene: VWA3B was added
gene: VWA3B was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VWA3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA3B were set to 26157035
Phenotypes for gene: VWA3B were set to Spinocerebellar ataxia, autosomal recessive 22 MIM#616948
Review for gene: VWA3B was set to AMBER
Added comment: A homozygous missense variant was identified in 3 brothers from a single consanguineous Japanese family with autosomal recessive cerebellar ataxia. Transfection of the mutant VWA3B protein into several different cultured cell lines resulted in decreased cell viability.
Sources: Expert list
Mendeliome v0.2952 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2950 PLD3 Bryony Thompson gene: PLD3 was added
gene: PLD3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PLD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLD3 were set to 29053796; 30312375; 30312384
Phenotypes for gene: PLD3 were set to Spinocerebellar ataxia 46 MIM#617770
Review for gene: PLD3 was set to AMBER
Added comment: A heterozygous missense was identified in 8 affected members of a single family with spinocerebellar ataxia, and supporting in vitro functional assays.
Sources: Expert list
Mendeliome v0.2944 POC5 Bryony Thompson gene: POC5 was added
gene: POC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POC5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POC5 were set to 25642776; 29272404
Phenotypes for gene: POC5 were set to Idiopathic scoliosis; retinitis pigmentosa; short stature; microcephaly; recurrent glomerulonephritis
Review for gene: POC5 was set to GREEN
Added comment: Three heterozygous missense variants identified in three families segregating with idiopathic scoliosis, and supporting zebrafish models for each of the missense variants.
Also, one case reported with retinitis pigmentosa, short stature, microcephaly, and recurrent glomerulonephritis with a homozygous truncating variant and a supporting zebrafish model.
Sources: Literature
Mendeliome v0.2943 KIF3B Paul De Fazio gene: KIF3B was added
gene: KIF3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIF3B were set to hepatic fibrosis; retinitis pigmentosa; postaxial polydactyly
Review for gene: KIF3B was set to AMBER
Added comment: 2 families reported with missense variants, one de novo and one segregating in a six-generation pedigree. Functional studies in zebrafish showed the variants result in impaired rhodopsin trafficking.
Sources: Literature
Mendeliome v0.2943 SPATA13 Ain Roesley gene: SPATA13 was added
gene: SPATA13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPATA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPATA13 were set to PMID: 32339198
Phenotypes for gene: SPATA13 were set to primary angle-closure glaucoma
Added comment: PMID: 32339198; 10 unrelated probands with missense except for 2 families with inframe del of 9bp.
Sources: Literature
Mendeliome v0.2943 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Mendeliome v0.2943 CNP Kristin Rigbye gene: CNP was added
gene: CNP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNP were set to 32128616; 12590258
Phenotypes for gene: CNP were set to Hypomyelinating leukodystrophy
Review for gene: CNP was set to AMBER
Added comment: Single consanguineous family described with homozygous missense in affected child (additional two affected deceased offspring unavailable for testing; healthy carrier parents and sibling).
Loss of protein by Western blot and defect in F-actin structure and organization observed in patient fibroblasts.
Deficiency of CNP in mouse has previously been shown to cause a lethal white matter neurodegenerative phenotype (PMID: 12590258), similar to the phenotype observed in this family.
Sources: Literature
Mendeliome v0.2943 SLC12A2 Ee Ming Wong reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32294086; Phenotypes: Congenital, severe to profound hearing loss, minor motor developmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2943 TRIM71 Elena Savva reviewed gene: TRIM71: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29983323, 32168371, 30975633; Phenotypes: Hydrocephalus, congenital communicating, 1 618667; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2943 TRIM71 Elena Savva gene: TRIM71 was added
gene: TRIM71 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633
Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667
Mode of pathogenicity for gene: TRIM71 was set to Other
Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child.

PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder

PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism.
Sources: Literature
Mendeliome v0.2943 RIMS2 Paul De Fazio gene: RIMS2 was added
gene: RIMS2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIMS2 were set to 32470375
Review for gene: RIMS2 was set to GREEN
Added comment: Segregates with Syndromic Congenital Cone-Rod Synaptic Disease in 7 individuals across 4 families. Some functional studies related to insulin secretion but they are non-significant.
Sources: Literature
Mendeliome v0.2942 RBM7 Bryony Thompson gene: RBM7 was added
gene: RBM7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RBM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBM7 were set to 27193168
Phenotypes for gene: RBM7 were set to SMA-like spinal motor neuropathy; dHMN/dSMA
Review for gene: RBM7 was set to AMBER
Added comment: Single case with a homozygote variant, with functional assays in patient fibroblasts. Also, supporting zebrafish model.
Sources: Expert list
Mendeliome v0.2940 SORD Seb Lunke gene: SORD was added
gene: SORD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to 32367058
Phenotypes for gene: SORD were set to isolated hereditary neuropathy
Review for gene: SORD was set to GREEN
gene: SORD was marked as current diagnostic
Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG
(p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state
Sources: Literature
Mendeliome v0.2938 KCNJ8 Zornitza Stark Mode of inheritance for gene: KCNJ8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2936 KCNJ8 Zornitza Stark reviewed gene: KCNJ8: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2934 KCNE3 Zornitza Stark Mode of inheritance for gene: KCNE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2932 KCNE3 Zornitza Stark reviewed gene: KCNE3: Rating: RED; Mode of pathogenicity: None; Publications: 29959160; Phenotypes: Brugada syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2932 DNAH6 Elena Savva gene: DNAH6 was added
gene: DNAH6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH6 were set to PMID: 26918822
Phenotypes for gene: DNAH6 were set to Heterotaxy, Azoospermia
Review for gene: DNAH6 was set to AMBER
Added comment: PMID: 26918822 - zebrafish model has disrupted motile cilia and cilia length, with some body axis defects within embryos. Transfected human cells also had defective motile cilia and cilia width.
Two patients with heterotaxy, one homozygous (missense), the other heterozygous (missense), but the heterozygous carrier has an additional known PCD mutation in DNA1.

Summary: 1 convincing patient with animal model
Sources: Literature
Mendeliome v0.2931 XIST Zornitza Stark Mode of inheritance for gene: XIST was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 XIST Zornitza Stark reviewed gene: XIST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-inactivation, familial skewed, MIM# 300087; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2930 SYNE2 Zornitza Stark Phenotypes for gene: SYNE2 were changed from to Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999
Mendeliome v0.2927 SYNE2 Bryony Thompson reviewed gene: SYNE2: Rating: RED; Mode of pathogenicity: None; Publications: 32184094, 17761684; Phenotypes: Emery-Dreifuss muscular dystrophy 5, autosomal dominant MIM#612999; Mode of inheritance: None
Mendeliome v0.2926 PRKAG3 Bryony Thompson reviewed gene: PRKAG3: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17878938, 10818001; Phenotypes: increased glycogen content in skeletal muscle; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2926 PAH Elena Savva reviewed gene: PAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phenylketonuria 261600, [Hyperphenylalaninemia, non-PKU mild] 261600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2925 ANO5 Zornitza Stark Phenotypes for gene: ANO5 were changed from to Gnathodiaphyseal dysplasia MIM#166260; Miyoshi muscular dystrophy 3 MIM#613319; Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307
Mendeliome v0.2924 ANO5 Zornitza Stark Mode of inheritance for gene: ANO5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2920 MYF6 Bryony Thompson reviewed gene: MYF6: Rating: RED; Mode of pathogenicity: None; Publications: 11053684; Phenotypes: Centronuclear myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2919 MTMR14 Bryony Thompson reviewed gene: MTMR14: Rating: RED; Mode of pathogenicity: None; Publications: 17008356; Phenotypes: {Centronuclear myopathy, autosomal, modifier of} MIM#160150; Mode of inheritance: Unknown
Mendeliome v0.2918 ANO5 Bryony Thompson reviewed gene: ANO5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32112655; Phenotypes: Gnathodiaphyseal dysplasia MIM#166260, Miyoshi muscular dystrophy 3 MIM#613319, Muscular dystrophy, limb-girdle, autosomal recessive 12 MIM#611307; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2916 DNAJB11 Zornitza Stark Mode of inheritance for gene: DNAJB11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2915 DNAJB11 Zornitza Stark reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706351, 29777155; Phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2913 GPR143 Zornitza Stark Mode of inheritance for gene: GPR143 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2910 ELP1 Zornitza Stark Mode of inheritance for gene: ELP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2909 GPR143 Teresa Zhao reviewed gene: GPR143: Rating: GREEN; Mode of pathogenicity: None; Publications: 30555098, 29761529; Phenotypes: congenital nystagmus 6, MIM 300814, ty[e I ocular albinism, Nettleship-Falls type, MIM 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2909 ELP1 Bryony Thompson reviewed gene: ELP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11179008, 32296180; Phenotypes: Dysautonomia, familial MIM#223900, paediatric medulloblastoma; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2907 SNRNP200 Zornitza Stark Mode of inheritance for gene: SNRNP200 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2906 SNRNP200 Ain Roesley reviewed gene: SNRNP200: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31260034, 29320387, 23847139, 27735924; Phenotypes: Retinitis pigmentosa 33 (MIM# 610359); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2906 ALOXE3 Zornitza Stark Phenotypes for gene: ALOXE3 were changed from to Ichthyosis, congenital, autosomal recessive 3, MIM#606545
Mendeliome v0.2904 ALOXE3 Zornitza Stark Mode of inheritance for gene: ALOXE3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2902 ALOXE3 Chern Lim reviewed gene: ALOXE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 31046801, 26370990; Phenotypes: Ichthyosis, congenital, autosomal recessive 3, MIM#606545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2900 STK36 Zornitza Stark Mode of inheritance for gene: STK36 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2898 STK36 Zornitza Stark reviewed gene: STK36: Rating: RED; Mode of pathogenicity: None; Publications: 28543983; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2896 NME8 Zornitza Stark Mode of inheritance for gene: NME8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2891 TFAP2A Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2890 TFAP2A Teresa Zhao reviewed gene: TFAP2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23578821, 21204207, 21728810, 21539471; Phenotypes: Branchiooculofacial syndrome, MIM 113620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2890 NME8 Elena Savva reviewed gene: NME8: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 17360648; Phenotypes: Ciliary dyskinesia, primary, 6 610852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2889 ARL3 Bryony Thompson gene: ARL3 was added
gene: ARL3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ARL3 were set to 30269812; 16565502; 26964041; 30932721
Phenotypes for gene: ARL3 were set to Joubert syndrome 35 MIM#618161; Retinitis pigmentosa 83 MIM#618173
Review for gene: ARL3 was set to GREEN
Added comment: 4 patients from 2 unrelated consanguineous families with a phenotype resembling Joubert syndrome with homozygous missense mutations affecting the same residue (R149C, R149H), and supporting in vitro functional assays. All reported cases had rod-cone dystrophy. An Arl3 null mouse model has a ciliary disease phenotype affecting the kidney, biliary tract, pancreas, and retina.
Two unrelated families with retinitis pigmentosa segregating the same heterozygous missense variant (Y90C).
Sources: Expert list
Mendeliome v0.2882 CEP19 Bryony Thompson gene: CEP19 was added
gene: CEP19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP19 were set to 29127258; 24268657
Phenotypes for gene: CEP19 were set to Morbid obesity and spermatogenic failure MIM#615703
Review for gene: CEP19 was set to AMBER
Added comment: A consanguineous Arab family with morbid obesity and infertility with a homozygous predicted null variant, and a mouse model that recapitulates the phenotype. Another homozygous variant has been identified in a consanguineous Bardet Beidl syndrome.
Sources: Literature
Mendeliome v0.2880 DALRD3 Zornitza Stark gene: DALRD3 was added
gene: DALRD3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DALRD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DALRD3 were set to 32427860
Phenotypes for gene: DALRD3 were set to Epileptic encephalopathy
Review for gene: DALRD3 was set to AMBER
Added comment: Two individuals reported with same homozygous nonsense variant, functional data.
Sources: Literature
Mendeliome v0.2873 KRAS Zornitza Stark Mode of inheritance for gene: KRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2871 GAA Zornitza Stark Mode of inheritance for gene: GAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2868 HEXA Zornitza Stark Mode of inheritance for gene: HEXA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2865 DHX30 Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2862 FAT1 Zornitza Stark Mode of inheritance for gene: FAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 KRAS Elena Savva reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23059812, 17056636; Phenotypes: Arteriovenous malformation of the brain, somatic 108010, Bladder cancer, somatic 109800, Breast cancer, somatic 114480, Cardiofaciocutaneous syndrome 2 615278, Gastric cancer, somatic 137215, Leukemia, acute myeloid 601626, . Lung cancer, somatic 211980, Noonan syndrome 3 609942, Pancreatic carcinoma, somatic 260350, RAS-associated autoimmune leukoproliferative disorder 614470, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic 163200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2861 GAA Elena Savva reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease II 232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 HEXA Elena Savva reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31388111; Phenotypes: [Hex A pseudodeficiency] 272800, GM2-gangliosidosis, several forms 272800, Tay-Sachs disease 272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2861 DHX30 Elena Savva reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29100085; Phenotypes: Neurodevelopmental disorder with severe motor impairment and absent language, 617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2860 PITPNM3 Bryony Thompson reviewed gene: PITPNM3: Rating: RED; Mode of pathogenicity: None; Publications: 17377520, 22405330, 20590364; Phenotypes: Cone-rod dystrophy 5 MIM#600977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2860 FAT1 Ee Ming Wong reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30862798; Phenotypes: facial dysmorphism, colobomatous microphthalmia, ptosis, syndactyly with or without nephropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2859 JARID2 Zornitza Stark gene: JARID2 was added
gene: JARID2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JARID2 were set to 23294540
Phenotypes for gene: JARID2 were set to Intellectual disability
Review for gene: JARID2 was set to AMBER
Added comment: Emerging evidence that haploinsufficiency causes neurodevelopmental phenotypes, mostly based on CNV data to date.
Sources: Expert Review
Mendeliome v0.2855 ADIPOR1 Zornitza Stark Mode of inheritance for gene: ADIPOR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2853 ADIPOR1 Zornitza Stark reviewed gene: ADIPOR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27655171, 26662040; Phenotypes: Retinitis pigmentosa; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2853 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Mendeliome v0.2851 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2850 TRIP12 Zornitza Stark reviewed gene: TRIP12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27848077, 28251352; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2847 CLCC1 Bryony Thompson gene: CLCC1 was added
gene: CLCC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CLCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCC1 were set to 30157172
Phenotypes for gene: CLCC1 were set to Retinitis pigmentosa 32
Review for gene: CLCC1 was set to AMBER
Added comment: A presumptive Pakastani founder mutation (c.75C>A, p.D25E) was identified in 8 consanguineous arRP families. A knockout zebrafish model and a Clcc1 +/- mouse model had a supporting retinal phenotype.
Sources: Expert list
Mendeliome v0.2844 B9D1 Zornitza Stark Mode of inheritance for gene: B9D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2840 BBIP1 Zornitza Stark Mode of inheritance for gene: BBIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2836 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2833 PACS1 Ain Roesley reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2832 STARD7 Zornitza Stark gene: STARD7 was added
gene: STARD7 was added to Mendeliome. Sources: Expert list
STR tags were added to gene: STARD7.
Mode of inheritance for gene: STARD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STARD7 were set to 11701600; 24114805; 31664034
Phenotypes for gene: STARD7 were set to Epilepsy, familial adult myoclonic, 2, 607876
Mode of pathogenicity for gene: STARD7 was set to Other
Review for gene: STARD7 was set to GREEN
Added comment: 158 individuals from 22 families reported with heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene.
Sources: Expert list
Mendeliome v0.2828 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Zornitza Stark reviewed gene: PDXK: Rating: AMBER; Mode of pathogenicity: None; Publications: 31187503; Phenotypes: Axonal polyneuropathy, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 DHCR7 Crystle Lee reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23059950; Phenotypes: Smith-Lemli-Opitz syndrome (MIM#270400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2825 PDXK Russell Gear gene: PDXK was added
gene: PDXK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to (PMID: 31187503)
Phenotypes for gene: PDXK were set to Axonal polyneuropathy; optic atrophy
Review for gene: PDXK was set to RED
Added comment: Currently two unrelated families with axonal polyneuropathy and optic atrophy described in the same paper, with bi-allelic PDXK pathogenic variants. Functional work in the same paper includes work on patient derived fibroblasts, measurement of an axonal damage biomarker (NFL protein), and response to PLP supplementation treatment.

Need one further unrelated family to upgrade to green?
Sources: Literature
Mendeliome v0.2823 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2820 TMEM107 Zornitza Stark Mode of inheritance for gene: TMEM107 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2819 TMEM107 Zornitza Stark reviewed gene: TMEM107: Rating: GREEN; Mode of pathogenicity: None; Publications: 26518474, 26595381, 26123494; Phenotypes: Meckel syndrome 13 (MIM#617562), Orofaciodigital syndrome XVI (MIM#617563), Joubert syndrome 29 617562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2816 ALPL Zornitza Stark Mode of inheritance for gene: ALPL was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2814 LRRC56 Zornitza Stark reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 39, MIM# 618254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2814 ALPL Melanie Marty reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19500388, 23688511; Phenotypes: Hypophosphatasia, adult 146300 (AD, AR), Hypophosphatasia, childhood 241510 AR, Hypophosphatasia, infantile 241500 AR, Odontohypophosphatasia 146300 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2814 LRRC56 Elena Savva gene: LRRC56 was added
gene: LRRC56 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LRRC56 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC56 were set to PMID: 30388400
Phenotypes for gene: LRRC56 were set to Ciliary dyskinesia, primary, 39 618254
Added comment: PMID: 30388400 - used protist null model to show abnormal ciliary beatings, replicated the phenotype when the protist was transfected with mutant allele observed in a patient.
3 unrelated families reported with either homozygous splice, missense or chet (nonsense/splice). Patients exhibited phenotypes including chronic respiratory/ear infections, situs inversus
Sources: Expert list
Mendeliome v0.2812 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2809 TCF7L1 Zornitza Stark Mode of inheritance for gene: TCF7L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2807 TCF7L1 Naomi Baker reviewed gene: TCF7L1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26764381; Phenotypes: Congenital hypopituitarism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2806 GFI1B Bryony Thompson gene: GFI1B was added
gene: GFI1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFI1B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GFI1B were set to 24325358; 23927492; 28041820; 11825872
Phenotypes for gene: GFI1B were set to Bleeding disorder, platelet-type, 17 MIM#187900
Review for gene: GFI1B was set to GREEN
Added comment: Three families with a heterozygous variant and one case with a homozygous variant, with supporting in vitro functional assays. A null mouse model contained erythroid and megakaryocytic precursors arrested in their development.
Sources: Literature
Mendeliome v0.2805 MOGS Elena Savva reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31925597; Phenotypes: Congenital disorder of glycosylation, type IIb 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2805 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Mendeliome v0.2803 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2800 NODAL Zornitza Stark Mode of inheritance for gene: NODAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2798 NODAL Zornitza Stark reviewed gene: NODAL: Rating: RED; Mode of pathogenicity: None; Publications: 9354794, 19064609; Phenotypes: Heterotaxy, visceral, 5 (MIM#270100); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2796 PIH1D3 Zornitza Stark Mode of inheritance for gene: PIH1D3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2795 PIH1D3 Zornitza Stark reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 24421334, 28176794; Phenotypes: Ciliary dyskinesia, primary, 36, X-linked (MIM#300991); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2793 COL10A1 Zornitza Stark Mode of inheritance for gene: COL10A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2792 COL10A1 Zornitza Stark reviewed gene: COL10A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15880705, 31633898; Phenotypes: Metaphyseal chondrodysplasia, Schmid type, MIM#156500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2791 CEP112 Bryony Thompson gene: CEP112 was added
gene: CEP112 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP112 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP112 were set to 31654588
Phenotypes for gene: CEP112 were set to Acephalic spermatozoa; infertility
Review for gene: CEP112 was set to AMBER
Added comment: Two unrelated cases reported with acephalic spermatozoa, one case with a homozygous nonsense variant and the other case with biallelic missense variants. CEP112 expression was significantly reduced in one of the cases, suggesting loss of function as a mechanism of disease.
Sources: Literature
Mendeliome v0.2790 PRKD1 Kristin Rigbye reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2790 KPNA7 Alison Yeung gene: KPNA7 was added
gene: KPNA7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KPNA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KPNA7 were set to 24045845; 32179771
Phenotypes for gene: KPNA7 were set to Epilepsy; intellectual disability
Review for gene: KPNA7 was set to RED
Added comment: Single family with two siblings
Sources: Literature
Mendeliome v0.2788 NR4A2 Zornitza Stark gene: NR4A2 was added
gene: NR4A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NR4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR4A2 were set to 31428396; 30504930; 29770430; 12756136; 9092472
Phenotypes for gene: NR4A2 were set to Intellectual disability; epilepsy
Review for gene: NR4A2 was set to GREEN
Added comment: Over ten individuals reported with mono-allelic variants in this gene and neurodevelopmental phenotypes. Link with dementia/Parkinson's disease disputed.
Sources: Literature
Mendeliome v0.2786 TOMM70 Zornitza Stark gene: TOMM70 was added
gene: TOMM70 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOMM70 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TOMM70 were set to 31907385; 32356556
Phenotypes for gene: TOMM70 were set to Severe anaemia, lactic acidosis, developmental delay; White matter abnormalities, developmental delay, regression, movement disorder
Review for gene: TOMM70 was set to AMBER
Added comment: TOM70 is a member of the TOM complex that transports cytosolic proteins into mitochondria.
Bi-allelic disease: one individual reported with compound heterozygous variants in TOMM70 [c.794C>T (p.T265M) and c.1745C>T (p.A582V)]. Clinical features included severe anaemia, lactic acidosis, and developmental delay. Some functional data: in vitro cell model compensatory experiments.
Monoallelic disease: de novo mono allelic variants in the C-terminal region of TOMM70 reported in two individuals. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset, with one experiencing episodes of regression. Some functional data.
Sources: Expert list
Mendeliome v0.2782 CUL3 Zornitza Stark Mode of inheritance for gene: CUL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2781 CUL3 Zornitza Stark reviewed gene: CUL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22495309, 22914163, 25363760, 27824329, 32341456; Phenotypes: Pseudohypoaldosteronism, type IIE 614496, Intellectual disability, Autism, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2778 EGR2 Zornitza Stark Mode of inheritance for gene: EGR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2777 EGR2 Zornitza Stark reviewed gene: EGR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 11523566, 31852952; Phenotypes: Charcot-Marie-Tooth disease, type 1D 607678 AD, Dejerine-Sottas disease 145900 AD, AR, Hypomyelinating neuropathy, congenital, 1 605253 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2775 GAS2L2 Zornitza Stark Mode of inheritance for gene: GAS2L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2773 GAS2L2 Zornitza Stark reviewed gene: GAS2L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30665704; Phenotypes: Ciliary dyskinesia, primary, 41 (MIM # 618449); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2771 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21.
Functional analysis showed decreased activity in response to FGF21 and FGF8.
KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Mendeliome v0.2769 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Mendeliome v0.2767 UGDH Zornitza Stark gene: UGDH was added
gene: UGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Review for gene: UGDH was set to GREEN
Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors
Sources: Literature
Mendeliome v0.2764 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Literature
Mendeliome v0.2761 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2759 TNRC6B Zornitza Stark edited their review of gene: TNRC6B: Added comment: 17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).; Changed rating: GREEN; Changed publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Changed phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2758 CDC42BPB Zornitza Stark gene: CDC42BPB was added
gene: CDC42BPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Review for gene: CDC42BPB was set to GREEN
Added comment: 14 individuals with missense and loss-of-function CDC42BPB variants reported. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. Most variants occurred as de novo events (11/14) while inheritance was not available for few (3/14).
Sources: Literature
Mendeliome v0.2755 DNAJB13 Zornitza Stark Mode of inheritance for gene: DNAJB13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2753 DNAJB13 Zornitza Stark reviewed gene: DNAJB13: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486783; Phenotypes: Ciliary dyskinesia, primary, 34, MIM# 617091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2753 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from to Heterotaxy, visceral, 2, autosomal 605376
Mendeliome v0.2751 CFC1 Zornitza Stark Mode of inheritance for gene: CFC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2750 CFC1 Zornitza Stark reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31633655, 18162845, 25423076, 11062482; Phenotypes: Heterotaxy, visceral, 2, autosomal 605376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2750 CFAP53 Zornitza Stark Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive 614779
Mendeliome v0.2748 CFAP53 Zornitza Stark Mode of inheritance for gene: CFAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2747 CFAP53 Zornitza Stark reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 28621423, 22577226, 26531781; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive 614779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2745 TTC25 Zornitza Stark Mode of inheritance for gene: TTC25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2743 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2742 CFAP43 Elena Savva gene: CFAP43 was added
gene: CFAP43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592
Added comment: aka WDR96

PMID: 31884020 - animal models (mouse, frog) demonstrate the protein localizes in ciliary axoneme and is involved in MOTILE cilia movement. LOF CFAP43 caused mucus acucmulation in airways, impaired spermatogenesis and hydrocephalus.

PMID: 28552195 - 3x chet (bilallelic PTCs or chet PTC/missense) with abnormal sperm motility. Null mouse models were also infertile.

PMID: 31004071 - one family with a heterozygous nonsense and AD inheritance of late onset hydrocephaly (checked in Mutalyzer, variant is NMD predicted). Abnormal cilia observed from mucosa sample. Null mice also show abnormal sperm and dilation of brain ventricles.

PMID: 29449551 - reports an additional 10 patients with either homozygous PTCs or chet PTC/missense who were infertile with flagella defects

Summary: single report of AD hydrocephaly
Sources: Literature
Mendeliome v0.2740 MYLK2 Zornitza Stark Mode of inheritance for gene: MYLK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2738 MYLK2 Zornitza Stark reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: 11733062, 24082139, 25825456, 20301725; Phenotypes: Cardiomyopathy, hypertrophic, 1, digenic, 192600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2736 CDX2 Zornitza Stark Mode of inheritance for gene: CDX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2734 CDX2 Zornitza Stark reviewed gene: CDX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29177441; Phenotypes: Persistent cloaca; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2732 TAPT1 Zornitza Stark Mode of inheritance for gene: TAPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2730 TAPT1 Zornitza Stark reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type (MIM#616897); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2727 C11orf70 Zornitza Stark Mode of inheritance for gene: C11orf70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2726 C11orf70 Zornitza Stark reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: None; Publications: 29727693, 29727692; Phenotypes: Ciliary dyskinesia, primary, 38, MIM# 618063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2724 ARMC9 Zornitza Stark Mode of inheritance for gene: ARMC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2720 ARMC4 Zornitza Stark Mode of inheritance for gene: ARMC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2719 ARMC4 Zornitza Stark reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31765523, 23849778; Phenotypes: Ciliary dyskinesia, primary, 23, MIM# 615451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2719 ACVR2B Zornitza Stark Phenotypes for gene: ACVR2B were changed from to Heterotaxy, visceral, 4, autosomal 613751
Mendeliome v0.2717 ACVR2B Zornitza Stark Mode of inheritance for gene: ACVR2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2715 ACVR2B Zornitza Stark reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2715 ACVR2B Elena Savva reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9916847, 30622330, 21864452; Phenotypes: Heterotaxy, visceral, 4, autosomal 613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2715 NID1 Zornitza Stark Phenotypes for gene: NID1 were changed from to Dandy-Walker malformation and occipital cephalocele; Hydrocephalus with or without seizures
Mendeliome v0.2713 NID1 Zornitza Stark Mode of inheritance for gene: NID1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2712 NID1 Zornitza Stark reviewed gene: NID1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23674478, 25558065, 12480912, 30773799; Phenotypes: Dandy-Walker malformation and occipital cephalocele, Hydrocephalus with or without seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2710 DARS Zornitza Stark Mode of inheritance for gene: DARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2709 DARS Zornitza Stark reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25527264, 23643384; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2707 CCDC65 Zornitza Stark Mode of inheritance for gene: CCDC65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2706 CCDC65 Zornitza Stark reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23991085, 24094744; Phenotypes: Ciliary dyskinesia, primary, 27, MIM# 615504; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2704 C21orf59 Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2703 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2701 WISP3 Zornitza Stark Mode of inheritance for gene: WISP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2700 WISP3 Zornitza Stark reviewed gene: WISP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10471507; Phenotypes: Arthropathy, progressive pseudorheumatoid, of childhood, MIM# 208230, Spondyloepiphyseal dysplasia tarda with progressive arthropathy, MIM# 208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2698 ATP5E Zornitza Stark Mode of inheritance for gene: ATP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2696 ATP5E Zornitza Stark reviewed gene: ATP5E: Rating: AMBER; Mode of pathogenicity: None; Publications: 20566710, 27626380, 20026007; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2694 ATP5D Zornitza Stark Mode of inheritance for gene: ATP5D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2693 ATP5D Zornitza Stark reviewed gene: ATP5D: Rating: GREEN; Mode of pathogenicity: None; Publications: 29478781; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, MIM# 618120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2691 ATP5A1 Zornitza Stark Mode of inheritance for gene: ATP5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2689 ATP5A1 Zornitza Stark reviewed gene: ATP5A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23599390; Phenotypes: Combined oxidative phosphorylation deficiency 22 616045, Mitochondrial complex V (ATP synthase) deficiency nuclear type 4, 615228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2687 GLDC Zornitza Stark Mode of inheritance for gene: GLDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2686 GLDC Crystle Lee reviewed gene: GLDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 27362913; Phenotypes: Glycine encephalopathy (MIM#605899); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2686 CD4 Zornitza Stark reviewed gene: CD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 31781092; Phenotypes: Absence of CD4+ T cells, exuberant, relapsing, treatment-refractory warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2686 TNK2 Zornitza Stark Mode of inheritance for gene: TNK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2683 TNK2 Zornitza Stark Mode of inheritance for gene: TNK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2681 MAN2B2 Zornitza Stark gene: MAN2B2 was added
gene: MAN2B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018
Phenotypes for gene: MAN2B2 were set to Congenital disorder of glycosylation; immunodeficiency
Review for gene: MAN2B2 was set to RED
Added comment: Single individual reported.
Sources: Literature
Mendeliome v0.2680 TNK2 Elena Savva reviewed gene: TNK2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID 27977884, 23686771, 31517310; Phenotypes: late onset infantile epilepsy, Mayer-Rokitansky-Küster-Hauser syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2678 RIPK1 Zornitza Stark Mode of inheritance for gene: RIPK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2677 RIPK1 Zornitza Stark reviewed gene: RIPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30026316, 30591564, 31213653, 31827280; Phenotypes: Immunodeficiency 57, MIM#618108; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2676 PIK3CG Zornitza Stark gene: PIK3CG was added
gene: PIK3CG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3CG were set to 32001535; 31554793
Phenotypes for gene: PIK3CG were set to Immune dysregulation; HLH-like; childhood-onset antibody defects; cytopenias; T lymphocytic pneumonitis and colitis
Review for gene: PIK3CG was set to GREEN
Added comment: Two individuals with complex immunological phenotypes reported and a mouse model.
Sources: Literature
Mendeliome v0.2674 RC3H1 Zornitza Stark gene: RC3H1 was added
gene: RC3H1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RC3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RC3H1 were set to 31636267
Phenotypes for gene: RC3H1 were set to Relapsing HLH
Review for gene: RC3H1 was set to RED
Added comment: Single individual with bi-allelic LoF variant and relapsing HLH reported, some functional data.
Sources: Literature
Mendeliome v0.2671 IFNG Zornitza Stark Mode of inheritance for gene: IFNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2669 IFNG Zornitza Stark reviewed gene: IFNG: Rating: RED; Mode of pathogenicity: None; Publications: 32163377; Phenotypes: Mendelian susceptibility to mycobacterial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2669 ITPKB Zornitza Stark gene: ITPKB was added
gene: ITPKB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPKB were set to 31987846
Phenotypes for gene: ITPKB were set to Severe combined immunodeficiency, absent T cells, present B cells and NK cells
Review for gene: ITPKB was set to RED
Added comment: Single individual with homozygous bi-allelic LoF variant reported.
Sources: Literature
Mendeliome v0.2668 PSMB10 Zornitza Stark gene: PSMB10 was added
gene: PSMB10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057
Phenotypes for gene: PSMB10 were set to Autoinflammatory syndrome
Review for gene: PSMB10 was set to RED
Added comment: PSMB10 is part of the immunoproteasome, and other components cause auto inflammatory disorders. Single individual with homozygous missense variant reported.
Sources: Literature
Mendeliome v0.2666 ABHD12 Zornitza Stark Mode of inheritance for gene: ABHD12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2664 AAAS Zornitza Stark Mode of inheritance for gene: AAAS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2663 NOS2 Zornitza Stark Phenotypes for gene: NOS2 were changed from to {Malaria, resistance to} 611162; Disseminated CMV disease
Mendeliome v0.2660 NOS2 Zornitza Stark reviewed gene: NOS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12433515, 31995689; Phenotypes: {Malaria, resistance to} 611162, Disseminated CMV disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2659 SNORA31 Zornitza Stark gene: SNORA31 was added
gene: SNORA31 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SNORA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SNORA31 were set to 31806906
Phenotypes for gene: SNORA31 were set to Susceptibility to HSV1 encephalitis
Review for gene: SNORA31 was set to GREEN
Added comment: Five unrelated individuals reported with rare missense variants in this gene, functional data to support susceptibility to herpes simplex encephalitis.
Sources: Expert list
Mendeliome v0.2656 TCOF1 Zornitza Stark Mode of inheritance for gene: TCOF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2655 TCOF1 Zornitza Stark reviewed gene: TCOF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12444270, 15150774, 21951868; Phenotypes: Treacher Collins syndrome 1, MIM# 154500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2653 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2651 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2647 CTSA Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2643 PI4KA Zornitza Stark Mode of inheritance for gene: PI4KA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2641 PI4KA Zornitza Stark reviewed gene: PI4KA: Rating: AMBER; Mode of pathogenicity: None; Publications: 25855803; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2639 CDK5 Zornitza Stark Mode of inheritance for gene: CDK5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2637 CDK5 Zornitza Stark reviewed gene: CDK5: Rating: RED; Mode of pathogenicity: None; Publications: 25560765; Phenotypes: Lissencephaly 7 with cerebellar hypoplasia, MIM# 616342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2636 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Mendeliome v0.2635 CTSA Zornitza Stark reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31177426; Phenotypes: Galactosialidosis, MIM# 256540, Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2634 CDK19 Zornitza Stark gene: CDK19 was added
gene: CDK19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK19 were set to 32330417
Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy
Review for gene: CDK19 was set to GREEN
Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data.
Sources: Literature
Mendeliome v0.2632 MNS1 Zornitza Stark gene: MNS1 was added
gene: MNS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MNS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MNS1 were set to 31534215; 30148830
Phenotypes for gene: MNS1 were set to Heterotaxy; male infertility
Review for gene: MNS1 was set to GREEN
Added comment: Eight families reported altogether, three LoF variants. Four Amish families share same homozygous founder variant, and some of the other reported families are consanguineous and share another founder variant. A reported female with a third variant, also had a homozygous variant in DNAH5 with a blended phenotype postulated.
Sources: Literature
Mendeliome v0.2630 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
Added comment: Seventeen individuals with 46,XY gonadal dysgenesis reported in two studies.
Sources: Literature
Mendeliome v0.2626 RAMP2 Zornitza Stark gene: RAMP2 was added
gene: RAMP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAMP2 were set to 31000793
Phenotypes for gene: RAMP2 were set to Primary open angle glaucoma
Review for gene: RAMP2 was set to AMBER
Added comment: Six variants identified in 16 of 4763 POAG patients from large cohorts; none identified in 10,953 control individuals. Some functional data.
Sources: Literature
Mendeliome v0.2624 MEPE Zornitza Stark gene: MEPE was added
gene: MEPE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPE were set to 30287925
Phenotypes for gene: MEPE were set to hereditary congenital facial paresis; otosclerosis
Review for gene: MEPE was set to AMBER
Added comment: Single four-generation family reported with variant in this gene segregating nonprogressive HCFP and mixed hearing loss (HL). Damaging variants (truncating/frameshift) found to be enriched in otosclerosis cohort (p = 0.0006–0.0060).
Sources: Literature
Mendeliome v0.2623 PAICS Zornitza Stark gene: PAICS was added
gene: PAICS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAICS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAICS were set to 31600779
Phenotypes for gene: PAICS were set to Polyhydramnios; multiple congenital abnormalities
Review for gene: PAICS was set to RED
Added comment: Two sibs from single family reported with homozygous missense variant. Functional data to demonstrate effect on protein function.
Sources: Literature
Mendeliome v0.2620 GALM Hazel Phillimore gene: GALM was added
gene: GALM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to PMID: 30451973; 30910422
Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia
Review for gene: GALM was set to GREEN
Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia.
In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973)
In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)
Sources: Literature
Mendeliome v0.2620 POLR3GL Paul De Fazio gene: POLR3GL was added
gene: POLR3GL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR3GL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3GL were set to 31089205; 31695177
Phenotypes for gene: POLR3GL were set to endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Review for gene: POLR3GL was set to AMBER
gene: POLR3GL was marked as current diagnostic
Added comment: Biallelic canonical splice variants were identified in monozygotic twins and another individual with similar phenotypes from 2 unrelated families. Variants were inherited from carrier parents. RNA studies confirmed exon skipping occurs in all affected individuals.

A separate study identified a homozygous nonsense variant in an individual with features of Neonatal progeroid syndrome/Wiedemann–Rautenstrauch syndrome. Quantitative PCR showed reduction in mRNA suggestive of NMD.
Sources: Literature
Mendeliome v0.2620 TSPEAR Zornitza Stark Phenotypes for gene: TSPEAR were changed from to Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180
Mendeliome v0.2618 TSPEAR Zornitza Stark Mode of inheritance for gene: TSPEAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2614 PDGFRB Zornitza Stark Mode of inheritance for gene: PDGFRB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2611 TSPEAR Chern Lim changed review comment from: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families. Functional study supported LoF. (PMIDs: 27736875, 30046887); to: Still a rare disease gene for ectodermal dysplasia but has been reported in at least 3 unrelated families in 2 papers. Functional study supported LoF. (PMIDs: 27736875, 30046887)
Mendeliome v0.2611 TSPEAR Chern Lim reviewed gene: TSPEAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27736875, 30046887; Phenotypes: Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2611 PDGFRB Ee Ming Wong reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30573803, 26279204; Phenotypes: Premature aging syndrome, Penttinen type, 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: Y-linked inheritance pattern. Complete segregation of a missense variant demonstrated in 9 affected males in a 5-generation pedigree. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio changed review comment from: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature; to: 9 affected males in a single 5-generation pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2611 TBL1Y Paul De Fazio gene: TBL1Y was added
gene: TBL1Y was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TBL1Y was set to Other
Publications for gene: TBL1Y were set to 30341416
Phenotypes for gene: TBL1Y were set to Hearing loss
Review for gene: TBL1Y was set to RED
gene: TBL1Y was marked as current diagnostic
Added comment: 9 affected males in a single pedigree described with Y-linked inheritance pattern. Functional studies show the missense variant causes reduced protein stability. The gene has restricted expression in the cochlea and prostate.
Sources: Literature
Mendeliome v0.2610 DGCR8 Chern Lim gene: DGCR8 was added
gene: DGCR8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGCR8 were set to 31805011
Phenotypes for gene: DGCR8 were set to Early-onset multinodular goiter and schwannomatosis
Review for gene: DGCR8 was set to RED
Added comment: A germline missense variant segregates in one family with autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter (MNG) with schwannomatosis. The missense is also a recurrent somatic missense variant in Wilms tumour. (PMID:31805011)
Sources: Literature
Mendeliome v0.2608 TDRD7 Zornitza Stark Mode of inheritance for gene: TDRD7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 TDRD7 Ee Ming Wong reviewed gene: TDRD7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28837160, 21436445; Phenotypes: cataract, glaucoma, nonobstructive azoospermia, arrested spermatogenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 FOXF2 Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Previous names for FOXF2 include FKHL6 and FREAC2.
Sources: Literature
Mendeliome v0.2607 FOXF2 Hazel Phillimore gene: FOXF2 was added
gene: FOXF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to PMID: 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature
Mendeliome v0.2605 COL13A1 Zornitza Stark Mode of inheritance for gene: COL13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2604 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317; primary familial brain calcifications (PFBC); ataxia; dysarthria; cerebellar atrophy; akinetic-hypertonic syndrome
Mendeliome v0.2602 COL13A1 Hazel Phillimore reviewed gene: COL13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31081514, 28369367, 20844119; Phenotypes: Myasthenic syndrome, congenital, 19 (OMIM #616720); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2602 KIAA1161 Hazel Phillimore reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29910000, 31009047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive (OMIM #618317), primary familial brain calcifications (PFBC), ataxia, dysarthria, cerebellar atrophy, akinetic-hypertonic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2602 CACNB4 Zornitza Stark changed review comment from: One multigenerational family and supportive animal model data.; to: One multigenerational family with ataxia and supportive animal model data.
Mendeliome v0.2598 WDR83OS Ee Ming Wong gene: WDR83OS was added
gene: WDR83OS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR83OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR83OS were set to PMID: 30250217
Phenotypes for gene: WDR83OS were set to Cholestasis
Review for gene: WDR83OS was set to RED
Added comment: - 1 consanguineous family with 3 affected individuals found to carry a homozygous splice site variant in WDR83OS
- The variant results in an aberrant truncated RNA transcript as demonstrated by RT-PCR
Sources: Literature
Mendeliome v0.2598 LSR Zornitza Stark reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: 32303357, 30250217; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2597 LSR Zornitza Stark reviewed gene: LSR: Rating: GREEN; Mode of pathogenicity: None; Publications: 32303357; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2595 LSR Ee Ming Wong reviewed gene: LSR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32303357, 30250217; Phenotypes: Intrahepatic cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2593 USP53 Zornitza Stark reviewed gene: USP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 32124521; Phenotypes: Cholestasis, deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2592 LSR Ee Ming Wong gene: LSR was added
gene: LSR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LSR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSR were set to PMID: 30250217
Phenotypes for gene: LSR were set to transient neonatal cholestasis; intellectual disability; short stature
Review for gene: LSR was set to RED
Added comment: 1 individual from 1 consanguineous family carrying a homozygous missense variant in LSR
Sources: Literature
Mendeliome v0.2591 USP53 Ee Ming Wong gene: USP53 was added
gene: USP53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP53 were set to PMID: 30250217
Phenotypes for gene: USP53 were set to Deafness
Review for gene: USP53 was set to RED
Added comment: 1 consanguineous family carrying a homozygous truncating variant in USP53
Sources: Literature
Mendeliome v0.2591 PPM1F Ee Ming Wong gene: PPM1F was added
gene: PPM1F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPM1F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPM1F were set to PMID: 30250217
Phenotypes for gene: PPM1F were set to sclerosing cholangitis; short stature; hypothyroidism; abnormal tongue pigmentation
Review for gene: PPM1F was set to RED
Added comment: 1 consanguineous family found to carry a homozygous missense variant in PPM1F
Sources: Literature
Mendeliome v0.2589 SPEF2 Zornitza Stark reviewed gene: SPEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31942643; Phenotypes: Spermatogenic failure 43, MIM#618751, Primary ciliary dyskinesia-like phenotype; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2588 KLC2 Zornitza Stark gene: KLC2 was added
gene: KLC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC2 were set to 26385635
Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541
Review for gene: KLC2 was set to GREEN
Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing.
Sources: Expert Review
Mendeliome v0.2584 KIF12 Zornitza Stark reviewed gene: KIF12: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250217, 30976738; Phenotypes: Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2583 ALPK1 Zornitza Stark gene: ALPK1 was added
gene: ALPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 31053777
Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Review for gene: ALPK1 was set to AMBER
Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Mendeliome v0.2581 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Mendeliome v0.2580 KIF12 Ee Ming Wong gene: KIF12 was added
gene: KIF12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF12 were set to PMID: 30250217; 30976738
Phenotypes for gene: KIF12 were set to Prenatal cholestasis; High Gamma-Glutamyltransferase (GGT)
Review for gene: KIF12 was set to AMBER
gene: KIF12 was marked as current diagnostic
Added comment: > 3 unrelated families,but they are all consanguineous families
Sources: Literature
Mendeliome v0.2579 CSGALNACT1 Zornitza Stark reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 31325655; Phenotypes: Congenital disorder of glycosylation, skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2579 UBAP1 Zornitza Stark Phenotypes for gene: UBAP1 were changed from Spastic paraplegia 80, autosomal dominant 618418 to Childhood-onset hereditary spastic paraplegia; Spastic paraplegia 80, autosomal dominant 618418
Mendeliome v0.2577 UBAP1 Zornitza Stark reviewed gene: UBAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31696996; Phenotypes: Childhood-onset hereditary spastic paraplegia, Spastic paraplegia 80, autosomal dominant 618418; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2577 RHOA Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy
Mendeliome v0.2575 RHOA Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31821646; Phenotypes: hypopigmented areas of the skin, dental anomalies, body asymmetry, limb length discrepancy, MRI abnormalities; Mode of inheritance: Other
Mendeliome v0.2574 IQCE Zornitza Stark gene: IQCE was added
gene: IQCE was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Postaxial polydactyly
Review for gene: IQCE was set to GREEN
Added comment: Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects.
Sources: Literature
Mendeliome v0.2573 NKX2-3 Zornitza Stark gene: NKX2-3 was added
gene: NKX2-3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NKX2-3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKX2-3 were set to 31498527
Phenotypes for gene: NKX2-3 were set to Intestinal varicosities
Review for gene: NKX2-3 was set to RED
Added comment: Single multiplex family where truncating variant in this gene segregated with intestinal varicosities with a LOD score of 3.3. NKX2‐3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice.
Sources: Literature
Mendeliome v0.2570 RPSA Zornitza Stark Mode of inheritance for gene: RPSA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2569 RPSA Zornitza Stark reviewed gene: RPSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23579497, 31498527; Phenotypes: Asplenia, isolated congenital 271400, Idiopathic intestinal varices; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2566 CRAT Zornitza Stark gene: CRAT was added
gene: CRAT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRAT were set to 29395073; 31448845
Phenotypes for gene: CRAT were set to Neurodegeneration with brain iron accumulation 8, MIM# 617917; Leigh syndrome
Review for gene: CRAT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants, one with NBIA and one with Leigh syndrome phenotype.
Sources: Literature
Mendeliome v0.2565 CWF19L1 Zornitza Stark Phenotypes for gene: CWF19L1 were changed from to Spinocerebellar ataxia, autosomal recessive 17, MIM#616127; intellectual disability, developmental delay
Mendeliome v0.2563 CWF19L1 Zornitza Stark Mode of inheritance for gene: CWF19L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2562 CWF19L1 Zornitza Stark reviewed gene: CWF19L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25361784, 15981765, 26197978, 27016154, 30167849; Phenotypes: Spinocerebellar ataxia, autosomal recessive 17, MIM#616127, intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2561 B4GAT1 Zornitza Stark changed review comment from: Two families reported.; to: Two families reported and two animal models.
Mendeliome v0.2561 B4GAT1 Zornitza Stark Phenotypes for gene: B4GAT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287
Mendeliome v0.2559 B4GAT1 Zornitza Stark Mode of inheritance for gene: B4GAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2557 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23359570, 23877401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2556 THG1L Zornitza Stark edited their review of gene: THG1L: Changed rating: GREEN; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Mendeliome v0.2554 THG1L Zornitza Stark gene: THG1L was added
gene: THG1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THG1L were set to 27307223; 31168944; 30214071
Phenotypes for gene: THG1L were set to Spinocerebellar ataxia, autosomal recessive 28, MIM# 618800
Review for gene: THG1L was set to AMBER
Added comment: Five individuals from two Ashkenazi Jewish families with same homozygous missense variant, and another family ascertained through a large microcephaly cohort, also with SCA.
Sources: Literature
Mendeliome v0.2553 TRPV1 Zornitza Stark gene: TRPV1 was added
gene: TRPV1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRPV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPV1 were set to 29930394
Phenotypes for gene: TRPV1 were set to Susceptibility to malignant hyperthermia
Review for gene: TRPV1 was set to RED
Added comment: Two individuals reported with rare/novel missense variants in this gene, some functional data.
Sources: Literature
Mendeliome v0.2551 ZP2 Zornitza Stark gene: ZP2 was added
gene: ZP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZP2 were set to 30810869; 29895852
Phenotypes for gene: ZP2 were set to Female infertility
Review for gene: ZP2 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and thin zona pellucida.
Sources: Literature
Mendeliome v0.2550 RSRC1 Zornitza Stark edited their review of gene: RSRC1: Added comment: 17 additional individuals reported.; Changed rating: GREEN; Changed publications: 28640246, 29522154, 32227164; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 70, MIM# 618402
Mendeliome v0.2548 GALNT2 Zornitza Stark gene: GALNT2 was added
gene: GALNT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALNT2 were set to 32293671
Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation
Review for gene: GALNT2 was set to GREEN
Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities.
Sources: Literature
Mendeliome v0.2546 C7orf43 Zornitza Stark gene: C7orf43 was added
gene: C7orf43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C7orf43 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C7orf43 were set to 30715179
Phenotypes for gene: C7orf43 were set to Microcephaly 25, primary, autosomal recessive, MIM# 618351
Review for gene: C7orf43 was set to AMBER
Added comment: Single family reported: three affected siblings with homozygous truncating variant. Supportive zebrafish model.
Sources: Literature
Mendeliome v0.2543 PLPBP Zornitza Stark reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27912044, 31741821, 30668673; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM# 617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2540 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2539 GRIN2A Zornitza Stark reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30544257; Phenotypes: Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2538 TSEN34 Zornitza Stark Mode of inheritance for gene: TSEN34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2535 TSEN34 Zornitza Stark reviewed gene: TSEN34: Rating: RED; Mode of pathogenicity: None; Publications: 18711368; Phenotypes: Pontocerebellar hypoplasia type 2C, MIM# 612390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2533 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2532 TSEN54 Zornitza Stark reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia type 2A 277470, Pontocerebellar hypoplasia type 4 225753, Ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2527 GABRB2 Zornitza Stark Mode of inheritance for gene: GABRB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2526 NDE1 Zornitza Stark Added comment: Comment when marking as ready: The two OMIM phenotypes likely represent a spectrum of brain abnormalities associated with this gene.
Mendeliome v0.2524 NDE1 Zornitza Stark Mode of inheritance for gene: NDE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2521 CDC45 Zornitza Stark Mode of inheritance for gene: CDC45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2516 CHD4 Zornitza Stark Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2515 RASA1 Zornitza Stark Phenotypes for gene: RASA1 were changed from to Capillary malformation-arteriovenous malformation 1, MIM#608354
Mendeliome v0.2513 RASA1 Zornitza Stark Mode of inheritance for gene: RASA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2512 CFAP69 Zornitza Stark Phenotypes for gene: CFAP69 were changed from to Asthenoteratospermia (Impaired sperm motility; severe flagellar abnormalities (short, coiled, absent or irregular calibre))
Mendeliome v0.2510 CFAP69 Zornitza Stark Mode of inheritance for gene: CFAP69 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2507 ABCA4 Zornitza Stark Mode of inheritance for gene: ABCA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2504 TLK2 Zornitza Stark Mode of inheritance for gene: TLK2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2503 DYRK1A Zornitza Stark Phenotypes for gene: DYRK1A were changed from to Mental retardation, autosomal dominant 7 (MIM#614104)
Mendeliome v0.2501 DYRK1A Zornitza Stark Mode of inheritance for gene: DYRK1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2498 POLR1B Zornitza Stark Phenotypes for gene: POLR1B were changed from bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations to Treacher-Collins syndrome
Mendeliome v0.2496 POLR1B Zornitza Stark reviewed gene: POLR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31649276; Phenotypes: Treacher-Collins syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2494 SLC35D1 Zornitza Stark Mode of inheritance for gene: SLC35D1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2489 NDE1 Elena Savva reviewed gene: NDE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30637988; Phenotypes: ?Microhydranencephaly 605013, Lissencephaly 4 (with microcephaly) 614019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2489 GABRB2 Elena Savva reviewed gene: GABRB2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 27789573, 29100083; Phenotypes: Epileptic encephalopathy, infantile or early childhood, 2 617829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2486 STIM1 Zornitza Stark Mode of inheritance for gene: STIM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2485 MDM2 Belinda Chong reviewed gene: MDM2: Rating: RED; Mode of pathogenicity: None; Publications: 28846075; Phenotypes: ?Lessel-Kubisch syndrome 618681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2482 ORAI1 Zornitza Stark Mode of inheritance for gene: ORAI1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2481 RTTN Zornitza Stark Phenotypes for gene: RTTN were changed from to Microcephaly, short stature, and polymicrogyria with seizures, MIM# 614833; Intellectual disability; cerebral polymicrogyria; primary microcephaly; growth defects; congenital anomalies
Mendeliome v0.2479 RTTN Zornitza Stark Mode of inheritance for gene: RTTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2478 UBAP1 Zornitza Stark Phenotypes for gene: UBAP1 were changed from to Spastic paraplegia 80, autosomal dominant 618418
Mendeliome v0.2476 UBAP1 Zornitza Stark Mode of inheritance for gene: UBAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2470 ABCC1 Zornitza Stark gene: ABCC1 was added
gene: ABCC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ABCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC1 were set to 31273342
Phenotypes for gene: ABCC1 were set to Nonsyndromic hearing loss
Review for gene: ABCC1 was set to AMBER
Added comment: Total of 3 variants reported in 3 families, including 1 which segregates in a large family (10 affected) PMID: 31273342; Li 2019: Reported 3 different het missense in 3 families with postlingual ADNSHL. 1 missense segregated in a large Chinese family. This variant is present in gnomAD (10 hets), but onset noted to be in 2nd or 3rd decade of life. Functional studies performed. Other 2 variants reported absent in gnomAD. Amber rating in light of gnomad frequency of one of the reported variants.
Sources: Literature
Mendeliome v0.2467 GABRA1 Zornitza Stark Mode of inheritance for gene: GABRA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2466 SIGMAR1 Zornitza Stark Phenotypes for gene: SIGMAR1 were changed from to Amyotrophic lateral sclerosis 16, juvenile 614373; ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726; distal hereditary motor neuropathy of Jerash type (HMNJ)
Mendeliome v0.2464 SIGMAR1 Zornitza Stark Mode of inheritance for gene: SIGMAR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2463 ATOH7 Zornitza Stark Phenotypes for gene: ATOH7 were changed from to Persistent hyperplastic primary vitreous, autosomal recessive, MIM# 221900; microphthalmia; cataract; glaucoma; congenital retinal nonattachment
Mendeliome v0.2461 ATOH7 Zornitza Stark Mode of inheritance for gene: ATOH7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2459 GNAI2 Zornitza Stark reviewed gene: GNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27787898; Phenotypes: Syndromic intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2456 KLHL24 Zornitza Stark Mode of inheritance for gene: KLHL24 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2455 KLHL24 Zornitza Stark reviewed gene: KLHL24: Rating: GREEN; Mode of pathogenicity: None; Publications: 30715372; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2452 SEC31A Zornitza Stark Phenotypes for gene: SEC31A were changed from congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive to Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MIM# 618651; congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive
Mendeliome v0.2447 SMCHD1 Zornitza Stark Mode of inheritance for gene: SMCHD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2444 CDKL5 Zornitza Stark Mode of inheritance for gene: CDKL5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2441 AEBP1 Zornitza Stark Mode of inheritance for gene: AEBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 AEBP1 Zornitza Stark reviewed gene: AEBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29606302, 30668708, 30548383, 30759870; Phenotypes: Ehlers-Danlos syndrome, classic-like, 2, MIM# 618000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 SLC6A6 Chern Lim gene: SLC6A6 was added
gene: SLC6A6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC6A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC6A6 were set to 31345061; 31903486; 29886034
Phenotypes for gene: SLC6A6 were set to Early retinal degeneration; cardiomyopathy
Review for gene: SLC6A6 was set to AMBER
Added comment: Different homozygous missense variants in 2 unrelated consanguineous families with early retinal degeneration, some functional studies. Patients in one of the families also had cardiomyopathy. (PMIDs: 31345061, 31903486)

One dilated cardiomyopathy patient with a homozygous deletion at a splice site (PMID: 29886034).
Sources: Literature
Mendeliome v0.2440 MRPS14 Dean Phelan reviewed gene: MRPS14: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30358850; Phenotypes: perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 TMPRSS9 Chern Lim gene: TMPRSS9 was added
gene: TMPRSS9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMPRSS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMPRSS9 were set to 31943016
Phenotypes for gene: TMPRSS9 were set to autism spectrum disorder
Review for gene: TMPRSS9 was set to RED
Added comment: Association with Mendelian disease not established.

Is a candidate gene for autism spectrum disorder: single patient, compound heterozygous nonsense variants. Functional studies showed Tmprss9 gene is expressed in mouse brain, knockout mice had decreased social interest and social recognition. (PMID: 31943016)
Sources: Literature
Mendeliome v0.2440 MCAT Chern Lim gene: MCAT was added
gene: MCAT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCAT were set to 31915829
Phenotypes for gene: MCAT were set to progressive autosomal recessive optic neuropathy
Review for gene: MCAT was set to RED
Added comment: One family reported - a consanguineous family, two homozygous missense variants in both affected siblings. Functional studies showed both missense together have synergic impact on MCAT protein misfolding; p.(L81R) had more impact on MCAT protein expression reduction than did the p.(R212W); some study in conditional knockout mice. (PMID:31915829)
Sources: Literature
Mendeliome v0.2440 WIPI2 Melanie Marty edited their review of gene: WIPI2: Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.; Changed rating: RED; Changed phenotypes: Intellectual developmental disorder with short stature and variable skeletal anomalies 618453
Mendeliome v0.2440 ATOH7 Paul De Fazio changed review comment from: Segregates with disease in 3 consanguineous families from Pakistan/Turkey and one non-consanguineous family of Swiss origin. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation.; to: Segregates with disease in 3 consanguineous families from Pakistan/Turkey with global eye abnormalities, and one non-consanguineous family of Swiss origin with optic nerve hypoplasia. Functional effect was demonstrated in the latter family. The mouse homolog is required for retinal ganglion cell and optic nerve formation (in mice).
Mendeliome v0.2440 UBAP1 Ain Roesley reviewed gene: UBAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31203368; Phenotypes: hereditary spastic paraplegia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2440 RTTN Ee Ming Wong reviewed gene: RTTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30879067; Phenotypes: Intellectual disability, cerebral polymicrogyria, primary microcephaly, growth defects, congenital anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 CDKL5 Teresa Zhao reviewed gene: CDKL5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 2, MIM 300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.2440 STIM1 Natalie Tan reviewed gene: STIM1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31448844; Phenotypes: Myopathy, immunodeficiency; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2440 UBA2 Elena Savva gene: UBA2 was added
gene: UBA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Penetrance for gene: UBA2 were set to unknown
Review for gene: UBA2 was set to AMBER
Added comment: No OMIM phenotype

PMID: 31332306 - a single patient with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in patients with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance

PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Sources: Literature
Mendeliome v0.2440 ORAI1 Natalie Tan changed review comment from: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy); to: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a spectrum of myopathy covering tubular aggregate myopathy/TAM and Stormorken syndrome/STRMK (slowly progressive muscle weakness with variable multisystemic disease including non-specific dysmorphism, a/hyposplenia, ichthyosis, cytopenias)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)
Mendeliome v0.2440 ORAI1 Natalie Tan reviewed gene: ORAI1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31448844; Phenotypes: Progressive myopathy, contractures; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2440 REC114 Michelle Torres gene: REC114 was added
gene: REC114 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: REC114 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC114 were set to 30388401; 31704776
Phenotypes for gene: REC114 were set to Female infertility
Review for gene: REC114 was set to GREEN
Added comment: Three variants reported are either within or flanking exon 4.
- One hom patient (splice) had a miscarriage, 2 spontaneous complete hydatidiform moles, and 1 complete hydatidiform mole following intrauterine sperm injection (PMID: 30388401)
- Two hom unrelated patients from consanguineous families with abnormal pronuclear formation during fertilisation and subsequent early embrionic arrest resulting in female infertility. Both variants (1 missense and 1 splice) were shown to result in LoF (PMID: 31704776)
Sources: Literature
Mendeliome v0.2440 AGTPBP1 Kristin Rigbye reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30420557; Phenotypes: Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy, Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2439 C1orf194 Ain Roesley gene: C1orf194 was added
gene: C1orf194 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C1orf194 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C1orf194 were set to PMID: 31199454
Phenotypes for gene: C1orf194 were set to Charcot-Marie-Tooth
Review for gene: C1orf194 was set to AMBER
Added comment: PMID: 31199454; 2 missense variants in 2 large families segregating in an AD pattern. Mouse models for one of the variants (p.(Ile121Asn) led to impairments in moto and neuromuscular functions
Sources: Literature
Mendeliome v0.2439 SLC35D1 Teresa Zhao reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31423530, 19508970; Phenotypes: Schneckenbecken dysplasia, MIM 269250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2439 POLR1B Paul De Fazio gene: POLR1B was added
gene: POLR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR1B were set to 31649276
Phenotypes for gene: POLR1B were set to bilateral malar and mandibular hypoplasia; microtia; coloboma; downslanting palpebral fissures; conductive deafness; cleft palate; heart malformations
Review for gene: POLR1B was set to AMBER
gene: POLR1B was marked as current diagnostic
Added comment: 6 individuals with Treacher-Collins syndrome described: 3 with de novo variants, one inherited from a mosaic father, and two inherited from affected mothers. Knockdown in zebrafish mimics the phenotype.
Sources: Literature
Mendeliome v0.2437 CREB3L1 Zornitza Stark Mode of inheritance for gene: CREB3L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2436 WARS Naomi Baker gene: WARS was added
gene: WARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783.
Phenotypes for gene: WARS were set to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration
Review for gene: WARS was set to GREEN
Added comment: 14 patients from five families were reported to have WARS-related neuropathy across three publications. Expression studies of mutant demonstrated decreased protein when compared to wild-type.
Sources: Literature
Mendeliome v0.2432 CYLD Zornitza Stark Mode of inheritance for gene: CYLD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2429 PCDH19 Zornitza Stark Mode of inheritance for gene: PCDH19 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.2427 SLC9A7 Dean Phelan reviewed gene: SLC9A7: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30335141; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.2426 GFAP Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2423 COPA Zornitza Stark Mode of inheritance for gene: COPA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2422 DYRK1A Crystle Lee reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25707398, 31263215; Phenotypes: Mental retardation, autosomal dominant 7 (MIM#614104); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2422 COPA Zornitza Stark Mode of inheritance for gene: COPA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2421 TLK2 Teresa Zhao reviewed gene: TLK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:29861108, 29942082, 27479843, 23911319, 30559488, 29942082, 31558842; Phenotypes: Intellectual disability, MIM 618050, Neurodevelopmental disease; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2421 PLOD3 Alison Yeung Mode of inheritance for gene: PLOD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2419 FOXG1 Zornitza Stark Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2418 TBX6 Alison Yeung Mode of inheritance for gene: TBX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2418 SAMD12 Zornitza Stark Mode of inheritance for gene: SAMD12 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2416 ABCA4 Kristin Rigbye reviewed gene: ABCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 9054934, 30480703, 29847635, 29971439, 16103129, 30643219; Phenotypes: Cone-rod dystrophy 3, 604116, Fundus flavimaculatus, 248200, Retinal dystrophy, early-onset severe, 248200, Retinitis pigmentosa 19, 601718, Stargardt disease 1, 248200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2416 CFAP69 Ee Ming Wong reviewed gene: CFAP69: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29606301, 30415212; Phenotypes: Asthenoteratospermia (Impaired sperm motility, severe flagellar abnormalities (short, coiled, absent or irregular calibre)); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2416 RASA1 Chern Lim reviewed gene: RASA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14639529, 29891884, 24038909, 31300548; Phenotypes: Capillary malformation-arteriovenous malformation 1, MIM#608354; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2416 ADAMTS19 Alison Yeung Added comment: Comment on list classification: Two different homozygous variants in two consanguineous families. Animal model demonstrates cardiac phenotype
Await further reported families
Mendeliome v0.2413 YARS Zornitza Stark Mode of inheritance for gene: YARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2408 IGF1R Zornitza Stark Mode of inheritance for gene: IGF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2406 CHD4 Teresa Zhao reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31388190; Phenotypes: Sifrim-Hitz-Weiss syndrome, MIM 617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2405 SHANK3 Zornitza Stark Mode of inheritance for gene: SHANK3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2402 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2401 CPSF1 Kristin Rigbye changed review comment from: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892).
Sources: Literature; to: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (PMID: 30689892).
Sources: Literature
Mendeliome v0.2401 CPSF1 Kristin Rigbye gene: CPSF1 was added
gene: CPSF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CPSF1 were set to 30689892
Phenotypes for gene: CPSF1 were set to Myopia 27, 618827; high myopia; early-onset high myopiaHigh myopia
Review for gene: CPSF1 was set to GREEN
Added comment: 6 unrelated probands reported (3 nonsense, 1 frameshift, 1 splice, 1 missense) with variants all assumed to result in a loss of function. Variants were shown to be inherited from affected parents in 2 families. Gene-disease association was supported by knockdown of cpsf1 in zebrafish which caused abnormal ocular morphogenesis (30689892).
Sources: Literature
Mendeliome v0.2399 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2396 NAA10 Zornitza Stark Mode of inheritance for gene: NAA10 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.2395 CDC45 Teresa Zhao reviewed gene: CDC45: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31474763; Phenotypes: Meier-Gorlin syndrome 7, MIM 617063; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2393 WDR45 Zornitza Stark Mode of inheritance for gene: WDR45 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2392 GABRA1 Ain Roesley reviewed gene: GABRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11992121, 21714819, 24623842, 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes, idiopathic generalized Epilepsy, dravet syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2392 SIGMAR1 Michelle Torres reviewed gene: SIGMAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31511340; Phenotypes: ?Amyotrophic lateral sclerosis 16, juvenile 614373, ?Spinal muscular atrophy, distal, autosomal recessive, 2 605726, distal hereditary motor neuropathy of Jerash type (HMNJ); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2392 ATOH7 Paul De Fazio reviewed gene: ATOH7: Rating: GREEN; Mode of pathogenicity: None; Publications: 22068589, 22645276, 31696227, 11493566, 11493566; Phenotypes: microphthalmia, cataract, glaucoma, congenital retinal nonattachment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2392 GNAI2 Elena Savva gene: GNAI2 was added
gene: GNAI2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GNAI2 were set to PMID: 31036916
Phenotypes for gene: GNAI2 were set to Pituitary adenoma, ACTH-secreting, somatic; Ventricular tachycardia, idiopathic 192605; Syndromic developmental disorder
Review for gene: GNAI2 was set to AMBER
Added comment: Papers associating this gene to tachycardia are very old (pre 2000, OMIM).

PMID: 31036916 - a single de novo patient with syndromic developmental disorder

Summary: AMBER - one report, may be a coincidental de novo finding
Sources: Literature
Mendeliome v0.2390 SOD2 Zornitza Stark Mode of inheritance for gene: SOD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2387 ASCC1 Zornitza Stark Mode of inheritance for gene: ASCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2386 FEM1B Elena Savva gene: FEM1B was added
gene: FEM1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1B were set to PMID: 31036916
Phenotypes for gene: FEM1B were set to Syndromic global developmental delay
Review for gene: FEM1B was set to AMBER
Added comment: No OMIM phenotype

PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein.

Have selected AMBER for now - not sure if GeneMatcher findings can be used as a 3rd case
Sources: Literature
Mendeliome v0.2386 SMAD2 Zornitza Stark Phenotypes for gene: SMAD2 were changed from to Aortic and arterial aneurysmal disease; connective tissue disease
Mendeliome v0.2384 RXFP2 Alison Yeung Added comment: Comment on list classification: Only single reported family with animal model reported. Both reviews to date are based on same publication. No new publications/reported cases since this one.
Mendeliome v0.2383 SMAD2 Zornitza Stark Mode of inheritance for gene: SMAD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2380 RXFP2 Zornitza Stark Mode of inheritance for gene: RXFP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2378 RXFP2 Zornitza Stark reviewed gene: RXFP2: Rating: RED; Mode of pathogenicity: None; Publications: 31167797, 20963592; Phenotypes: Cryptorchidism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2378 WIPI2 Melanie Marty gene: WIPI2 was added
gene: WIPI2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPI2 were set to 30968111
Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453
Review for gene: WIPI2 was set to AMBER
Added comment: Four homozygous patients from one consanguineous family with intellectual developmental, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.
Sources: Literature
Mendeliome v0.2378 SEC31A Hazel Phillimore gene: SEC31A was added
gene: SEC31A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEC31A were set to PMID: 30464055
Phenotypes for gene: SEC31A were set to congenital neurodevelopmental syndrome; spastic paraplegia; multiple contractures; profound developmental delay; epilepsy; failure to thrive
Review for gene: SEC31A was set to AMBER
Added comment: Frameshift. c.2776_2777, TA duplication, causing predicted p.A927fs*61 truncation and predicted NMD in 2 affected siblings in consanguineous Bedouin family with severe congenital neurological syndrome with spastic paraplegia, multiple contractures, profound developmental delay and convulsions. Failure to thrive. Lethal by age 4 years. Also had hearing defect, bilateral congenital cataract, horizontal nystagmus, with flat retina and optic atrophy. Supporting functional assays from knockout drosophila.
Sources: Literature
Mendeliome v0.2378 SLC44A1 Sebastian Lunke gene: SLC44A1 was added
gene: SLC44A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria
Review for gene: SLC44A1 was set to GREEN
Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial.
Sources: Literature
Mendeliome v0.2377 TBX6 Dean Phelan reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30307510, 31015262; Phenotypes: congenital vertebral malformations, congenital scoliosis, spondylocostal dysostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2377 SMCHD1 Teresa Zhao reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31600781; Phenotypes: Bosma arhinia microphthalmia syndrome, MIM 603457, Fascioscapulohumeral muscular dystrophy 2, digenic; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2377 CDKL5 Ain Roesley reviewed gene: CDKL5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27080038, 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes, Epileptic encephalopathy; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.2377 GSX2 Elena Savva gene: GSX2 was added
gene: GSX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSX2 were set to PMID: 31412107
Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646
Review for gene: GSX2 was set to GREEN
Added comment: PMID: 31412107 - 2 unrelated patients with homozygous mutations (nonsense, missense). Functional analysis of the missense in transfected HeLa cells demonstrated protein mislocalization and protein expression. Downstream gene expression was also reduced by both mutations.

Summary: GREEN - 2 patients and functional evidence
Sources: Literature
Mendeliome v0.2376 CREB3L1 Kristin Rigbye reviewed gene: CREB3L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24079343, 28817112, 29936144, 30657919; Phenotypes: Osteogenesis imperfecta, type XVI, 616229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2375 SPEF2 Chern Lim gene: SPEF2 was added
gene: SPEF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPEF2 were set to 31151990; 31278745; 31048344
Phenotypes for gene: SPEF2 were set to Spermatogenic failure 43, MIM#618751
Review for gene: SPEF2 was set to GREEN
gene: SPEF2 was marked as current diagnostic
Added comment: More than 3 unrelated families reported, all PTVs or splice variant. Functional studies showed SPEF2 protein levels were reduced in patients’ spermatozoa. (PMIDs: 31151990, 31278745, 31048344).
Sources: Literature
Mendeliome v0.2373 DHH Zornitza Stark Mode of inheritance for gene: DHH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2372 ACKR3 Elena Savva gene: ACKR3 was added
gene: ACKR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACKR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACKR3 were set to PMID: 3121183
Phenotypes for gene: ACKR3 were set to Oculomotor synkinesis
Review for gene: ACKR3 was set to AMBER
Added comment: No phenotype currently listed in OMIM

PMID: 3121183 - 1 family (3 siblings and a cousin) with congenital ptosis and oculomotor synkinesis. Mouse model reciprocated the phenotype. Functional assay using transfected HEK293 cells show protein mislocalization and lower binding affinity

Emerging gene-disease association
Sources: Literature
Mendeliome v0.2372 CYLD Kristin Rigbye reviewed gene: CYLD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835629, 16307661, 12950348, 19807742; Phenotypes: Brooke-Spiegler syndrome, 605041, Cylindromatosis, familial, 132700, Trichoepithelioma, multiple familial, 1, 601606, Frontotemporal dementia and amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2371 PCDH19 Ee Ming Wong reviewed gene: PCDH19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18469813, 30287595; Phenotypes: PCDH19-related epilepsy (early seizure onset, generalised or focused seizures), cognitive impairment; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.2369 MYCN Zornitza Stark Mode of inheritance for gene: MYCN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2368 GFAP Paul De Fazio reviewed gene: GFAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11138011, 12034785, 31004048, 15732097; Phenotypes: Leukodystrophy, macrocephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2367 CNNM4 Zornitza Stark Mode of inheritance for gene: CNNM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2366 ATM Zornitza Stark Mode of inheritance for gene: ATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2365 COPA Teresa Zhao reviewed gene: COPA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31455335, 30804679; Phenotypes: Autoimmune interstitial lung, joint, and kidney disease, MIM 616414; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2365 FOXG1 Ain Roesley reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18571142, 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2365 PLOD3 Sarah Pantaleo reviewed gene: PLOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18834968, 31129566, 30237576, 30463024; Phenotypes: Lysyl hydroxylase 3 deficiency, MIM#612394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2365 SAMD12 Melanie Marty gene: SAMD12 was added
gene: SAMD12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SAMD12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD12 were set to 30194086; 29507423
Phenotypes for gene: SAMD12 were set to Epilepsy, familial adult myoclonic, 1 601068
Review for gene: SAMD12 was set to GREEN
Added comment: Repeat expansions of intronic TTTCA and TTTTA motifs within SAMD12 have been identified in over 50 Japanese and Chinese families. Most families with affected individuals were heterozygous however 4 patients from 3 families had homozygous repeat expansions, which was associated with a more severe phenotype. Western blot analysis showed decreased levels of the protein in patient brains.
Sources: Literature
Mendeliome v0.2365 FUS Elena Savva gene: FUS was added
gene: FUS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FUS were set to PMID: 32281455; 20668259; 20385912
Phenotypes for gene: FUS were set to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia 608030; Essential tremor, hereditary, 4 614782
Mode of pathogenicity for gene: FUS was set to Other
Review for gene: FUS was set to GREEN
Added comment: PMID: 32281455 - Reports a case of Pediatric Amyotrophic Lateral Sclerosis. Reviews and shows multiple other reports of ALS casued by FUS

PMID: 20668259 - additional reports of ALS

PMID: 20385912 - postulated that disruption of this region may disrupt subcellular distribution of FUS, in turn affecting transcription and RNA processing and conferring a toxic gain of function.
Sources: Literature
Mendeliome v0.2365 TBX6 Sarah Pantaleo reviewed gene: TBX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 8954725, 20503311, 23335591, 25564734, 31015262; Phenotypes: Skeletal dysplasia, spondylocostal dysostosis, congenital scoliosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2365 UBE3A Ain Roesley reviewed gene: UBE3A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2365 ADAMTS19 Crystle Lee gene: ADAMTS19 was added
gene: ADAMTS19 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS19 were set to 31844321
Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease
Review for gene: ADAMTS19 was set to GREEN
Added comment: PMID: 31844321; Wünnemann 2020: 4 affected in unrelated 2 consanguineous family with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype
Sources: Expert Review
Mendeliome v0.2365 C9orf72 Elena Savva gene: C9orf72 was added
gene: C9orf72 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: C9orf72 were set to PMID: 30120348; 23284068
Phenotypes for gene: C9orf72 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Review for gene: C9orf72 was set to AMBER
Added comment: Possibly RED

Caused by expansion of GGGGCC repeats, dont know if these qualify for mendeliome
Sources: Literature
Mendeliome v0.2365 ELOVL1 Hazel Phillimore reviewed gene: ELOVL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30487246, 29496980; Phenotypes: ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness, optic atrophy, nystagmus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2364 YARS Dean Phelan reviewed gene: YARS: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 30304524, 29232904, 27633801, 19561293; Phenotypes: peripheral neuropathy, multisystem disease, CMT; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2364 CFAP65 Daniel Flanagan gene: CFAP65 was added
gene: CFAP65 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP65 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP65 were set to 31501240; 31413122
Phenotypes for gene: CFAP65 were set to Spermatogenic failure 40 618664
Penetrance for gene: CFAP65 were set to unknown
Review for gene: CFAP65 was set to GREEN
gene: CFAP65 was marked as current diagnostic
Added comment: 9 patients with multiple morphological abnormalities of the sperm flagella (MMAF) or completely immotile spermatozoa, in which, homozygous or compound heterozygous truncating CFAP65 variants were identified. Cfap65-mutated male mice displayed typical MMAF phenotypes with severe morphological abnormalities of the sperm flagella (PMID: 31501240, 31413122).
Sources: Literature
Mendeliome v0.2364 CAP2 Melanie Marty gene: CAP2 was added
gene: CAP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAP2 were set to 30518548
Phenotypes for gene: CAP2 were set to Dilated cardiomyopathy
Review for gene: CAP2 was set to AMBER
Added comment: 2 patients with dilated cardiomyopathy from 1 consanguineous family. The splice variant identified in this family was proven to cause exon skipping and functional studies showed protein level was reduced. A Cap2 knockout mouse model correlated with the clinical phenotype of DCM and cardiac conduction disease, but not the other effects on growth, viability, wound healing and eye development.
Sources: Literature
Mendeliome v0.2364 USP45 Alison Yeung Added comment: Comment on list classification: Two unrelated families
Functional studies in animal model recapitulate retinal phenotype
Mendeliome v0.2362 IGF1R Michelle Torres reviewed gene: IGF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586944; Phenotypes: Insulin-like growth factor I, resistance to 270450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2362 SHANK3 Ain Roesley reviewed gene: SHANK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2362 SCN1A Ee Ming Wong reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30368457, 12754708, 25754450; Phenotypes: Dravet Syndrome, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2362 SYCP2 Zornitza Stark gene: SYCP2 was added
gene: SYCP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYCP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYCP2 were set to 32092049; 31866047
Phenotypes for gene: SYCP2 were set to Male infertility
Review for gene: SYCP2 was set to GREEN
Added comment: Four individuals and a zebrafish model.
Sources: Literature
Mendeliome v0.2361 STXBP1 Ain Roesley reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2361 NAA10 Naomi Baker reviewed gene: NAA10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30842225.; Phenotypes: syndromic X-linked microphthalmia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.2361 WDR45 Ain Roesley reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30842224; Phenotypes: Rett syndrome, Rett-like phenotypes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2361 SOD2 Chern Lim reviewed gene: SOD2: Rating: RED; Mode of pathogenicity: None; Publications: 31494578; Phenotypes: Lethal neonatal dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 ASCC1 Sarah Pantaleo reviewed gene: ASCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30327447, 12077347, 26924529, 31880396, 26503956; Phenotypes: Arthrogryposis, congenital bone fractures, spinal muscular atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2361 SMAD2 Melanie Marty reviewed gene: SMAD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29967133; Phenotypes: Aortic and arterial aneurysmal disease, connective tissue disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2361 MYCN Ain Roesley reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21224895, 8470948, 30573562; Phenotypes: Feingold syndrome 1, megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2361 RXFP2 Teresa Zhao reviewed gene: RXFP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31167797, 20963592; Phenotypes: Cryptorchidism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2361 PKDCC Paul De Fazio gene: PKDCC was added
gene: PKDCC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKDCC were set to PMID:30478137; 19097194
Phenotypes for gene: PKDCC were set to Dysmorphism; shortening of extremities
Review for gene: PKDCC was set to AMBER
gene: PKDCC was marked as current diagnostic
Added comment: 2 ("apparently") unrelated individuals with homozygous LoF (1x nonsense, 1x canonical splice) variants reported. Their phenotype is similar to knockout mice.
Sources: Literature
Mendeliome v0.2361 DHH Naomi Baker reviewed gene: DHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31018998, 29471294, 11017805; Phenotypes: gonadal dysgenesis, minifascicular neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 MYCN Ain Roesley reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18470948, 21224895; Phenotypes: Feingold syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2361 TNFRSF21 Shannon Cowie gene: TNFRSF21 was added
gene: TNFRSF21 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: TNFRSF21 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNFRSF21 were set to PMID: 31189563
Phenotypes for gene: TNFRSF21 were set to high myopia
Review for gene: TNFRSF21 was set to RED
gene: TNFRSF21 was marked as current diagnostic
Added comment: Source: JMG review Oct 2019
Large Chinese family, including 12 patients with non-syndromic HM
Immunofluorescence assay indicated that it is strongly expressed in the mouse eye.
Sources: Other
Mendeliome v0.2361 USP45 Kristin Rigbye gene: USP45 was added
gene: USP45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP45 were set to 30573563
Phenotypes for gene: USP45 were set to Leber congenital amaurosis; retinal dystrophy
Review for gene: USP45 was set to GREEN
Added comment: 2 unrelated Chinese families reported with rare homozygous variants (one missense, one nonsense) and Leber congenital amaurosis. Animal knockout functional studies supported gene-disease association.

PMID: 30573563 "By analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45 were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45 transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45 mRNA. Moreover, targeted knockout of Usp45 in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA."
Sources: Literature
Mendeliome v0.2361 CNNM4 Ain Roesley reviewed gene: CNNM4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30705057; Phenotypes: Jalili syndrome (amelogenesis imperfecta, cone-rod dystrophy); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2361 ATM Kristin Rigbye reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30819809; Phenotypes: Ataxia-telangiectasia MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2360 BAZ2B Zornitza Stark gene: BAZ2B was added
gene: BAZ2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to 31999386; 28135719; 25363768
Phenotypes for gene: BAZ2B were set to Intellectual disability; autism
Review for gene: BAZ2B was set to GREEN
Added comment: Postulated as a candidate gene for ID/ASD by large-scale studies. Case series reports two individuals with small CNVs and and six with SNVs, mostly LoF type variants. Although the gene is generally intolerant of LoF, some LoF variants present in gnomad ?incomplete penetrance. Additional reported features were inconsistent
Sources: Literature
Mendeliome v0.2358 TPI1 Zornitza Stark gene: TPI1 was added
gene: TPI1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TPI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPI1 were set to Hemolytic anemia due to triosephosphate isomerase deficiency, MIM# 615512
Review for gene: TPI1 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.2356 EMG1 Zornitza Stark gene: EMG1 was added
gene: EMG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: EMG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMG1 were set to 19463982
Phenotypes for gene: EMG1 were set to Bowen-Conradi syndrome, MIM#211180
Review for gene: EMG1 was set to AMBER
Added comment: Founder mutation in Hutterite, D86G.
Sources: Expert list
Mendeliome v0.2354 EIF2AK4 Zornitza Stark gene: EIF2AK4 was added
gene: EIF2AK4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: EIF2AK4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EIF2AK4 were set to Pulmonary venoocclusive disease 2, MIM#234810
Review for gene: EIF2AK4 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.2352 AGBL5 Zornitza Stark gene: AGBL5 was added
gene: AGBL5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AGBL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGBL5 were set to 26720455; 26355662; 30925032
Phenotypes for gene: AGBL5 were set to Retinitis pigmentosa 75, MIM# 617023
Review for gene: AGBL5 was set to GREEN
Added comment: At least three unrelated families reported.
Sources: Expert list
Mendeliome v0.2350 CPT1C Bryony Thompson gene: CPT1C was added
gene: CPT1C was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CPT1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CPT1C were set to 25751282; 23973755
Phenotypes for gene: CPT1C were set to Spastic paraplegia 73, autosomal dominant MIM#616282
Review for gene: CPT1C was set to GREEN
Added comment: Two unrelated families dominant HSP and a supportive mouse model.
Sources: Expert list
Mendeliome v0.2348 ATP2B4 Bryony Thompson gene: ATP2B4 was added
gene: ATP2B4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP2B4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B4 were set to 25119969; 25798335; 29691679
Phenotypes for gene: ATP2B4 were set to Hereditary spastic paraplegia
Review for gene: ATP2B4 was set to AMBER
Added comment: One Chinese family segregating a missense variant with HSP and one HSP case with a assumed de novo nonsense variant. Supporting in vitro functional assays for the missense variant.
Sources: Expert list
Mendeliome v0.2343 SEC63 Zornitza Stark Mode of inheritance for gene: SEC63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2340 CYP1B1 Zornitza Stark Mode of inheritance for gene: CYP1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2339 DAG1 Zornitza Stark Phenotypes for gene: DAG1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Walker-Warburg syndrome and tectocerebellar dysgraphia
Mendeliome v0.2337 DAG1 Zornitza Stark Mode of inheritance for gene: DAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2334 DPYD Zornitza Stark Mode of inheritance for gene: DPYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2331 MFSD8 Zornitza Stark Mode of inheritance for gene: MFSD8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2329 NF1 Zornitza Stark Mode of inheritance for gene: NF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2328 TECTA Zornitza Stark Phenotypes for gene: TECTA were changed from to Deafness, autosomal recessive 21 603629; Deafness, autosomal dominant 8/12 601543
Mendeliome v0.2325 TECTA Zornitza Stark Mode of inheritance for gene: TECTA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2323 TRAPPC9 Zornitza Stark Phenotypes for gene: TRAPPC9 were changed from to Mental retardation, autosomal recessive 13, MIM# 613192
Mendeliome v0.2321 TRAPPC9 Zornitza Stark Mode of inheritance for gene: TRAPPC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2320 TRAPPC9 Zornitza Stark reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22549410, 20004765, 20004763; Phenotypes: Mental retardation, autosomal recessive 13, MIM# 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2317 SOS1 Zornitza Stark Mode of inheritance for gene: SOS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2316 F11 Zornitza Stark Phenotypes for gene: F11 were changed from to Factor XI deficiency, autosomal dominant 612416; Factor XI deficiency, autosomal recessive, MIM#612416
Mendeliome v0.2314 F11 Zornitza Stark Mode of inheritance for gene: F11 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.2311 MED13L Zornitza Stark Mode of inheritance for gene: MED13L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2309 CCT5 Bryony Thompson reviewed gene: CCT5: Rating: AMBER; Mode of pathogenicity: None; Publications: 16399879, 25124038, 25345891; Phenotypes: Neuropathy, hereditary sensory, with spastic paraplegia MIM#256840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2306 PROKR2 Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2305 PROKR2 Elena Savva reviewed gene: PROKR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:18826963, 29161432; Phenotypes: Hypogonadotropic hypogonadism 3 with or without anosmia 244200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2305 MED13L Elena Savva reviewed gene: MED13L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 29511999; Phenotypes: Mental retardation and distinctive facial features with or without cardiac defects 616789, Transposition of the great arteries, dextro-looped 1 608808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2305 F11 Elena Savva reviewed gene: F11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18446632, 15026311; Phenotypes: Factor XI deficiency, autosomal dominant 612416, Factor XI deficiency, autosomal recessive; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2305 SOS1 Elena Savva reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 25062969, 17143285, 17143282; Phenotypes: ?Fibromatosis, gingival, 1, 135300, Noonan syndrome 4, 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.2304 XRCC1 Bryony Thompson gene: XRCC1 was added
gene: XRCC1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XRCC1 were set to 28002403; 29472272
Phenotypes for gene: XRCC1 were set to Spinocerebellar ataxia, autosomal recessive 26 MIM#617633
Review for gene: XRCC1 was set to GREEN
Added comment: Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia.
Sources: Expert list
Mendeliome v0.2303 TRAPPC9 Elena Savva reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 13, 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2303 TECTA Elena Savva reviewed gene: TECTA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:22718023, 17136632, 31554319, 21520338; Phenotypes: Deafness, autosomal recessive 21 603629, Deafness, autosomal dominant 8/12 601543; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2303 NF1 Elena Savva reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukemia, juvenile myelomonocytic 607785, Neurofibromatosis, familial spinal 162210, Neurofibromatosis, type 1 162200, Neurofibromatosis-Noonan syndrome 601321, Watson syndrome 193520; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2302 TRPC3 Bryony Thompson gene: TRPC3 was added
gene: TRPC3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRPC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPC3 were set to 25477146; 19351902
Phenotypes for gene: TRPC3 were set to Spinocerebellar ataxia 41 MIM#616410
Mode of pathogenicity for gene: TRPC3 was set to Other
Review for gene: TRPC3 was set to AMBER
Added comment: A heterozygous gain-of function missense has been identified in a 40-year-old man with adult-onset spinocerebellar ataxia. A mouse model of dominant cerebellar ataxia, termed 'moonwalker', contains a gain-of-function variant in this gene.
Sources: Expert list
Mendeliome v0.2301 MFSD8 Elena Savva reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31006324; Phenotypes: Ceroid lipofuscinosis, neuronal, 7 610951, Macular dystrophy with central cone involvement 616170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 DPYD Elena Savva reviewed gene: DPYD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29152729; Phenotypes: 5-fluorouracil toxicity 274270, Dihydropyrimidine dehydrogenase deficiency 274270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 DAG1 Elena Savva reviewed gene: DAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29337005, 25503980; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818, Walker-Warburg syndrome and tectocerebellar dysgraphia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 CYP1B1 Elena Savva reviewed gene: CYP1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:21730847, 27243976; Phenotypes: Anterior segment dysgenesis 6, multiple subtypes, 617315, Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset, 231300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2301 SEC63 Elena Savva reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23209713, 20095989; Phenotypes: Polycystic liver disease 2 617004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.2300 SLC9A1 Zornitza Stark gene: SLC9A1 was added
gene: SLC9A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC9A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC9A1 were set to 25205112; 30018422; 25760855
Phenotypes for gene: SLC9A1 were set to Lichtenstein-Knorr syndrome, MIM# 616291
Review for gene: SLC9A1 was set to AMBER
Added comment: Two families with bi-allelic variants in this gene reported and combination of deafness and ataxia.
Sources: Expert list
Mendeliome v0.2298 MTCL1 Bryony Thompson gene: MTCL1 was added
gene: MTCL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MTCL1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MTCL1 were set to 30548255; 28283581
Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia
Review for gene: MTCL1 was set to AMBER
Added comment: Single case with a homozygous loss of function variant in a Polish study of early-onset cerebellar ataxia, and a single family with a single heterozygous missense (p.Val1435Met) identified in two family members with adult-onset spinocerebellar ataxia. Mtcl1 gene disruption in mice results in abnormal motor coordination with Purkinje cell degeneration
Sources: Expert list
Mendeliome v0.2296 ATG5 Bryony Thompson gene: ATG5 was added
gene: ATG5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG5 were set to 16625204; 26812546
Phenotypes for gene: ATG5 were set to Spinocerebellar ataxia, autosomal recessive 25 MIM#617584
Review for gene: ATG5 was set to AMBER
Added comment: A homozgyous variant was identified in a single family with two affected siblings. Mice deficient for Atg5 specifically in neural cells and Atg5 null Drosophila develop progressive deficits in motor function.
Sources: Expert list
Mendeliome v0.2295 IL18BP Zornitza Stark gene: IL18BP was added
gene: IL18BP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL18BP were set to 31213488
Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549
Review for gene: IL18BP was set to RED
Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis.
Sources: Expert list
Mendeliome v0.2292 IRF4 Zornitza Stark Mode of inheritance for gene: IRF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2290 IRF4 Zornitza Stark reviewed gene: IRF4: Rating: RED; Mode of pathogenicity: None; Publications: 29537367; Phenotypes: Whipple's disease, [Skin/hair/eye pigmentation, variation in, 8] 611724; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2290 ACOX2 Zornitza Stark Added comment: Comment when marking as ready: The ACOX2 gene encodes a peroxisomal branched-chain acyl-CoA oxidase involved in bile acid synthesis.
Mendeliome v0.2289 ACOX2 Zornitza Stark gene: ACOX2 was added
gene: ACOX2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6, 617308
Review for gene: ACOX2 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert Review
Mendeliome v0.2287 LARS Zornitza Stark gene: LARS was added
gene: LARS was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 28774368; 30349989; 22607940
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Review for gene: LARS was set to GREEN
gene: LARS was marked as current diagnostic
Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989.
Sources: NHS GMS
Mendeliome v0.2283 KCNJ11 Zornitza Stark Mode of inheritance for gene: KCNJ11 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2281 SIPA1L3 Bryony Thompson gene: SIPA1L3 was added
gene: SIPA1L3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SIPA1L3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SIPA1L3 were set to 28951961; 27993984; 25804400
Phenotypes for gene: SIPA1L3 were set to Cataract 45 MIM#616851
Review for gene: SIPA1L3 was set to AMBER
Added comment: A consanguineous German family segregating a homozygous nonsense mutation in two sisters with congenital cataracts (PMID: 25804400). Null Zebrafish, Xenopus and mouse models recapitulate the human cataract phenotype. A case with congenital cataracts as a feature of their condition harboured a de novo balanced chromosomal translocation, 46,XY,t(2;19)(q37.3;q13.1), where breakpoint mapping and sequencing showed a physical disruption of the 5′UTR of SIPA1L3 (PMID: 26231217). In a case with bilateral congenital cataracts a heterozygous missense (D148Y) was identified and in vitro functional assays of the variant resulted in abnormal actin morphology (PMID: 26231217).
Sources: Expert list
Mendeliome v0.2280 KCNJ11 Elena Savva reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: {Diabetes mellitus, type 2, susceptibility to} 125853, Diabetes mellitus, transient neonatal, 3 610582, Diabetes, permanent neonatal, with or without neurologic features 606176, Hyperinsulinemic hypoglycemia, familial, 2 601820, Maturity-onset diabetes of the young, type 13 616329 AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2279 SLC18A2 Zornitza Stark gene: SLC18A2 was added
gene: SLC18A2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to 23363473; 31240161; 26497564
Phenotypes for gene: SLC18A2 were set to Parkinsonism-dystonia, infantile, 2, MIM# 618049
Review for gene: SLC18A2 was set to GREEN
Added comment: At least three unrelated families reported, potential treatment implications
Sources: Expert Review
Mendeliome v0.2276 RNU4ATAC Zornitza Stark Mode of inheritance for gene: RNU4ATAC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2275 RNU4ATAC Ain Roesley reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23794361, 26522830, 30455926; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I (MIM# 210710), Roifman syndrome (MIM# 616651); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2273 IFT172 Zornitza Stark Mode of inheritance for gene: IFT172 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2272 KMT2E Zornitza Stark reviewed gene: KMT2E: Rating: GREEN; Mode of pathogenicity: None; Publications: 31079897; Phenotypes: O'Donnell-Luria-Rodan syndrome, MIM# 618512; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2270 KMT2E Zornitza Stark Mode of inheritance for gene: KMT2E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2267 MAP1B Zornitza Stark Mode of inheritance for gene: MAP1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2263 MAP3K7 Zornitza Stark Mode of inheritance for gene: MAP3K7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2262 MARS2 Zornitza Stark Phenotypes for gene: MARS2 were changed from to Combined oxidative phosphorylation deficiency 25, OMIM #616430; Spastic ataxia 3, autosomal recessive, OMIM #611390
Mendeliome v0.2260 MARS2 Zornitza Stark Mode of inheritance for gene: MARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2259 MARS2 Zornitza Stark changed review comment from: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV.; to: 1 family with 2 sibs with combined oxidative phosphorylation deficiency-25 (with ID) with compound heterozygous mutations in the MARS2 gene. Patient fibroblasts showed decreased activities of mitochondrial complexes I and IV, consistent with a mitochondrial translation defect. Immunoblot analysis showed reduced MARS2 protein levels as well as reduced levels of selected subunits of complexes I and IV. Spastic ataxia association: note complex chromosomal rearrangements rather than SNVs reported in group of 54 French Canadians.
Mendeliome v0.2257 MECOM Zornitza Stark Mode of inheritance for gene: MECOM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2254 MED17 Zornitza Stark Mode of inheritance for gene: MED17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2251 NEBL Zornitza Stark Mode of inheritance for gene: NEBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2249 NPHP3 Zornitza Stark Mode of inheritance for gene: NPHP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2248 NPHP3 Zornitza Stark reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Meckel syndrome 7, MIM# 267010, Nephronophthisis 3, MIM# 604387, Renal-hepatic-pancreatic dysplasia 1, MIM# 208540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2246 PAX1 Zornitza Stark reviewed gene: PAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32111619; Phenotypes: Otofaciocervical syndrome 2, MIM#615560, Syndromic SCID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2243 PAX1 Zornitza Stark Mode of inheritance for gene: PAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2242 PDE8B Zornitza Stark Phenotypes for gene: PDE8B were changed from to Striatal degeneration, autosomal dominant, MIM#609161
Mendeliome v0.2240 PDE8B Zornitza Stark Mode of inheritance for gene: PDE8B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2237 PIGG Zornitza Stark Phenotypes for gene: PIGG were changed from to Mental retardation, autosomal recessive 53, MIM#616917
Mendeliome v0.2235 PIGG Zornitza Stark Mode of inheritance for gene: PIGG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2232 PIGU Zornitza Stark Mode of inheritance for gene: PIGU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2231 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from to Mental retardation, autosomal recessive 55, MIM# 617051
Mendeliome v0.2229 PUS3 Zornitza Stark Mode of inheritance for gene: PUS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2228 RUBCN Zornitza Stark Phenotypes for gene: RUBCN were changed from to Spinocerebellar ataxia, autosomal recessive 15, MIM#615705
Mendeliome v0.2226 RUBCN Zornitza Stark Mode of inheritance for gene: RUBCN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2223 SHANK2 Zornitza Stark Mode of inheritance for gene: SHANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2222 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
Mendeliome v0.2220 SLC26A4 Zornitza Stark Mode of inheritance for gene: SLC26A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2217 SMPD4 Zornitza Stark Mode of inheritance for gene: SMPD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2216 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from to Coffin-Siris syndrome 9, MIM# 615866; Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.2214 SOX11 Zornitza Stark Mode of inheritance for gene: SOX11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2213 SOX11 Zornitza Stark changed review comment from: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data.
Sources: Expert list; to: Coffin-Siris syndrome: two individuals with de novo mono-allelic missense variants in this gene, mouse model.
CAKUT: Heterozygous variant in a patient with Coffin-Siris like syndrome and small kidney; but also rare variants identified in a non-syndromic CAKUT cohort with some functional data.
Sources: Expert list
Mendeliome v0.2213 SOX11 Zornitza Stark edited their review of gene: SOX11: Changed rating: GREEN; Changed phenotypes: Coffin-Siris syndrome 9, MIM# 615866, Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.2209 QRSL1 Zornitza Stark Mode of inheritance for gene: QRSL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2208 QRSL1 Zornitza Stark reviewed gene: QRSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 29440775, 30283131, 30642647; Phenotypes: Combined oxidative phosphorylation deficiency 40; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2206 PPCS Zornitza Stark Mode of inheritance for gene: PPCS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2204 PPCS Zornitza Stark reviewed gene: PPCS: Rating: AMBER; Mode of pathogenicity: None; Publications: 29754768; Phenotypes: Cardiomyopathy, dilated, 2C, MIM# 618189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2204 PET117 Zornitza Stark gene: PET117 was added
gene: PET117 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PET117 were set to 28386624
Phenotypes for gene: PET117 were set to Developmental delay; Regression; Complex IV deficiency
Review for gene: PET117 was set to RED
Added comment: Two siblings reported, some functional data. PET117 postulated to be a Complex IV assembly factor.
Sources: Expert list
Mendeliome v0.2203 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract to microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Mendeliome v0.2200 NUP188 Zornitza Stark edited their review of gene: NUP188: Added comment: Additional 6 unrelated individuals with bi-allelic LoF variants reported, promoted to Green.; Changed rating: GREEN; Changed publications: 32021605, 28726809, 32275884; Changed phenotypes: microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Mendeliome v0.2196 TBCD Zornitza Stark Mode of inheritance for gene: TBCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2195 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2188 WNT10A Zornitza Stark Phenotypes for gene: WNT10A were changed from to Odontoonychodermal dysplasia; Schopf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4
Mendeliome v0.2186 WNT10A Zornitza Stark Mode of inheritance for gene: WNT10A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2185 ZNF592 Zornitza Stark Phenotypes for gene: ZNF592 were changed from to SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 5
Mendeliome v0.2184 ZNF592 Zornitza Stark Mode of inheritance for gene: ZNF592 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2179 NME3 Zornitza Stark gene: NME3 was added
gene: NME3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NME3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NME3 were set to 30587587
Phenotypes for gene: NME3 were set to Hypotonia; Neurodegeneration; Abnormal mitochondrial dynamics
Review for gene: NME3 was set to RED
Added comment: Single individual reported. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics
Sources: Expert list
Mendeliome v0.2178 MRPS28 Zornitza Stark gene: MRPS28 was added
gene: MRPS28 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRPS28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS28 were set to 30566640
Phenotypes for gene: MRPS28 were set to Intrauterine growth retardation; developmental delay; dysmorphism
Review for gene: MRPS28 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2177 MRPS25 Zornitza Stark gene: MRPS25 was added
gene: MRPS25 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MRPS25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS25 were set to 31039582
Phenotypes for gene: MRPS25 were set to Dyskinetic cerebral palsy; Mitochondrial myopathy; Partial agenesis of the corpus callosum
Review for gene: MRPS25 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2176 MRPS23 Zornitza Stark Phenotypes for gene: MRPS23 were changed from Hepatic disease; Combined respiratory chain complex deficiencies to Hepatic disease; Combined respiratory chain complex deficienciesHepatic disease; Combined respiratory chain complex deficiencies; Cardiomyopathy; Tubulopathy; Lactic acidosis; Structural brain abnormalities
Mendeliome v0.2173 MRPS23 Zornitza Stark edited their review of gene: MRPS23: Added comment: Four families reported.; Changed rating: GREEN; Changed publications: 26741492, 17873122, 25663021, 28752220; Changed phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies, Cardiomyopathy, Tubulopathy, Lactic acidosis, Structural brain abnormalities
Mendeliome v0.2173 MIEF2 Zornitza Stark gene: MIEF2 was added
gene: MIEF2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MIEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIEF2 were set to 29361167
Phenotypes for gene: MIEF2 were set to Progressive muscle weakness; Exercise intolerance; Ragged red and COX negative fibres; Complex I and IV deficiency
Review for gene: MIEF2 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.2171 ERAL1 Zornitza Stark gene: ERAL1 was added
gene: ERAL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERAL1 were set to 28449065
Phenotypes for gene: ERAL1 were set to Perrault syndrome 6, MIM# 617565
Review for gene: ERAL1 was set to AMBER
Added comment: Three individuals from same small geographical location with homozygous missense variant in this gene, functional data.
Sources: Expert list
Mendeliome v0.2170 COX5A Zornitza Stark gene: COX5A was added
gene: COX5A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX5A were set to 2824752
Phenotypes for gene: COX5A were set to pulmonary arterial hypertension; lactic acidemia; failure to thrive; isolated complex IV deficiency
Review for gene: COX5A was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.2167 TRAF3IP2 Zornitza Stark Mode of inheritance for gene: TRAF3IP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2165 TRAF3IP2 Zornitza Stark reviewed gene: TRAF3IP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24120361, 31292894, 20660351; Phenotypes: Candidiasis, familial, 8, MIM# 615527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2163 TRAF3 Zornitza Stark Mode of inheritance for gene: TRAF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2161 TRAF3 Zornitza Stark reviewed gene: TRAF3: Rating: RED; Mode of pathogenicity: None; Publications: 20832341; Phenotypes: {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, MIM# 614849; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2159 TNFSF12 Zornitza Stark Mode of inheritance for gene: TNFSF12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2157 TNFSF12 Zornitza Stark reviewed gene: TNFSF12: Rating: RED; Mode of pathogenicity: None; Publications: 23493554; Phenotypes: Recurrent infections, poor antibody responses, decreased immunoglobulins; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2155 TNFRSF4 Zornitza Stark Mode of inheritance for gene: TNFRSF4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2153 TNFRSF4 Zornitza Stark reviewed gene: TNFRSF4: Rating: RED; Mode of pathogenicity: None; Publications: 23897980; Phenotypes: Immunodeficiency 16, MIM# 615593; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2151 TNFRSF13C Zornitza Stark Mode of inheritance for gene: TNFRSF13C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2149 TNFRSF13C Zornitza Stark reviewed gene: TNFRSF13C: Rating: AMBER; Mode of pathogenicity: None; Publications: 19666484, 26613719; Phenotypes: Immunodeficiency, common variable, 4, MIM# 613494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2144 THBD Zornitza Stark Mode of inheritance for gene: THBD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2142 THBD Zornitza Stark reviewed gene: THBD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29500241, 19625716; Phenotypes: {Hemolytic uremic syndrome, atypical, susceptibility to, 6}, MIM# 612926; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2141 TAPBP Zornitza Stark Mode of inheritance for gene: TAPBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2140 NXN Zornitza Stark Phenotypes for gene: NXN were changed from to Robinow syndrome, autosomal recessive 2 618529
Mendeliome v0.2138 NXN Zornitza Stark Mode of inheritance for gene: NXN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2137 NXN Zornitza Stark reviewed gene: NXN: Rating: GREEN; Mode of pathogenicity: None; Publications: 29276006; Phenotypes: Robinow syndrome, autosomal recessive 2 618529; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2135 TAPBP Zornitza Stark reviewed gene: TAPBP: Rating: RED; Mode of pathogenicity: None; Publications: 12149238; Phenotypes: Bare lymphocyte syndrome, type I, MIM# 604571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2133 SEMA3E Zornitza Stark Mode of inheritance for gene: SEMA3E was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2132 SEMA3E Zornitza Stark reviewed gene: SEMA3E: Rating: AMBER; Mode of pathogenicity: None; Publications: 15235037, 31691538, 31464029; Phenotypes: CHARGE syndrome, MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2130 RNF31 Zornitza Stark Mode of inheritance for gene: RNF31 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2128 RNF31 Zornitza Stark reviewed gene: RNF31: Rating: AMBER; Mode of pathogenicity: None; Publications: 26008899, 30936877; Phenotypes: Immune deficiency, Autoinflammation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2126 RHOH Zornitza Stark Mode of inheritance for gene: RHOH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2124 RHOH Zornitza Stark reviewed gene: RHOH: Rating: RED; Mode of pathogenicity: None; Publications: 22850876, 27574848; Phenotypes: {?Epidermodysplasia verruciformis, susceptibility to, 4}, MIM# 618307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2108 NFAT5 Zornitza Stark Mode of inheritance for gene: NFAT5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2106 NFAT5 Zornitza Stark reviewed gene: NFAT5: Rating: RED; Mode of pathogenicity: None; Publications: 25667416; Phenotypes: Recurrent infections, Autoimmune enterocolopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2104 MS4A1 Zornitza Stark Mode of inheritance for gene: MS4A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2102 MS4A1 Zornitza Stark reviewed gene: MS4A1: Rating: RED; Mode of pathogenicity: None; Publications: 20038800; Phenotypes: Immunodeficiency, common variable, 5, MIM# 613495; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2101 MASP2 Zornitza Stark Mode of inheritance for gene: MASP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2099 MASP2 Zornitza Stark reviewed gene: MASP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: MASP2 deficiency, MIM# 613791; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2096 IRF7 Zornitza Stark Mode of inheritance for gene: IRF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2094 IRF7 Zornitza Stark reviewed gene: IRF7: Rating: AMBER; Mode of pathogenicity: None; Publications: 25814066, 15800576; Phenotypes: Immunodeficiency 39, MIM# 616345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2092 IL21 Zornitza Stark Mode of inheritance for gene: IL21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2090 IL21 Zornitza Stark reviewed gene: IL21: Rating: RED; Mode of pathogenicity: None; Publications: 24746753; Phenotypes: Immunodeficiency, common variable, 11, MIM# 615767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2090 IL17F Zornitza Stark Phenotypes for gene: IL17F were changed from to Candidiasis, familial, 6, autosomal dominant, MIM# 613956
Mendeliome v0.2088 IL17F Zornitza Stark Mode of inheritance for gene: IL17F was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2086 IL17F Zornitza Stark reviewed gene: IL17F: Rating: RED; Mode of pathogenicity: None; Publications: 21350122; Phenotypes: Candidiasis, familial, 6, autosomal dominant, MIM# 613956; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2081 FCN3 Zornitza Stark Mode of inheritance for gene: FCN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2079 FCN3 Zornitza Stark reviewed gene: FCN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25662573, 22226667, 19535802, 20971976; Phenotypes: Immunodeficiency due to ficolin 3 deficiency, MIM# 613860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2077 FCGR3A Zornitza Stark Mode of inheritance for gene: FCGR3A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2075 FCGR3A Zornitza Stark reviewed gene: FCGR3A: Rating: AMBER; Mode of pathogenicity: None; Publications: 8874200, 23006327, 8608639; Phenotypes: Immunodeficiency 20, MIM# 615707; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2073 CR2 Zornitza Stark Mode of inheritance for gene: CR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2071 CR2 Zornitza Stark reviewed gene: CR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22035880, 26325596; Phenotypes: Immunodeficiency, common variable, 7, MIM# 614699; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2068 CFHR2 Zornitza Stark Mode of inheritance for gene: CFHR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2067 CFHR2 Zornitza Stark reviewed gene: CFHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24334459, 23728178, 20800271; Phenotypes: C3 glomerulopathy, C3G, Immune complex MPGN, IC-MPGN; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2065 CFB Zornitza Stark Mode of inheritance for gene: CFB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2063 CFB Zornitza Stark edited their review of gene: CFB: Changed rating: GREEN; Changed publications: 24152280, 17182750; Changed phenotypes: Complement factor B deficiency, MIM# 615561, {Hemolytic uremic syndrome, atypical, susceptibility to, 4} 612924; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2061 CFB Zornitza Stark Mode of inheritance for gene: CFB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2059 CFB Zornitza Stark reviewed gene: CFB: Rating: AMBER; Mode of pathogenicity: None; Publications: 24152280; Phenotypes: Complement factor B deficiency, MIM# 615561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2057 CD8A Zornitza Stark Mode of inheritance for gene: CD8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2055 CD8A Zornitza Stark reviewed gene: CD8A: Rating: AMBER; Mode of pathogenicity: None; Publications: 11435463, 17658607, 26563160; Phenotypes: CD8 deficiency, familial, MIM# 608957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2053 CD81 Zornitza Stark Mode of inheritance for gene: CD81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2051 CD81 Zornitza Stark reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 20237408; Phenotypes: Immunodeficiency, common variable, 6, MIM# 613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2047 BLOC1S6 Zornitza Stark Mode of inheritance for gene: BLOC1S6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2045 BLOC1S6 Zornitza Stark reviewed gene: BLOC1S6: Rating: AMBER; Mode of pathogenicity: None; Publications: 22461475, 21665000, 32245340; Phenotypes: Hermansky-Pudlak syndrome 9, MIM# 614171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2044 MIR140 Zornitza Stark gene: MIR140 was added
gene: MIR140 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: MIR140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR140 were set to 30804514; 31633310
Phenotypes for gene: MIR140 were set to Spondyloepiphyseal dysplasia, Nishimura type, MIM# 618618
Review for gene: MIR140 was set to GREEN
Added comment: Single clinical paper (30804514) reports variant in affected mother and child (de novo in mother) and in a separate unrelated female (de novo) with spondylo-epiphyseal dysplasia. Mouse model (21576357) deletion of gene causes impaired longitudinal bone growth. Separate mouse model studies by same authors as clinical paper above (30804514) showed phenotype of mice with same mutation in this gene consistent with the skeletal dysplasia features of patients with the n.24A-G mutation, suggestive of neomorphic effects (mutation produces both loss-of-function and gain-of-function effects.)
Sources: Expert Review
Mendeliome v0.2043 BCL10 Zornitza Stark reviewed gene: BCL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25365219, 32008135, 11163238, 12910267; Phenotypes: Immunodeficiency 37, MIM# 616098; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2043 APOL1 Zornitza Stark Mode of inheritance for gene: APOL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2039 APOL1 Zornitza Stark reviewed gene: APOL1: Rating: RED; Mode of pathogenicity: None; Publications: 29470556, 20647424, 24206458, 20635188; Phenotypes: {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2037 AP1S3 Zornitza Stark Mode of inheritance for gene: AP1S3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2035 AP1S3 Zornitza Stark reviewed gene: AP1S3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24791904, 27388993; Phenotypes: {Psoriasis 15, pustular, susceptibility to} 616106; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2033 KCNT2 Kristin Rigbye reviewed gene: KCNT2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29069600, 29740868, 32038177; Phenotypes: Epileptic encephalopathy, early infantile, 57, 617771, Epilepsy of infancy with migrating focal seizures (EIMFS); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2032 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from to Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380
Mendeliome v0.2030 PIEZO1 Zornitza Stark Mode of inheritance for gene: PIEZO1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2027 TBX19 Zornitza Stark Mode of inheritance for gene: TBX19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2026 TCF20 Zornitza Stark Phenotypes for gene: TCF20 were changed from to Developmental delay with variable intellectual impairment and behavioral abnormalities, AD, MIM#618430
Mendeliome v0.2024 TCF20 Zornitza Stark Mode of inheritance for gene: TCF20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2021 TFE3 Zornitza Stark Mode of inheritance for gene: TFE3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2020 TFE3 Zornitza Stark reviewed gene: TFE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30595499, 31833172; Phenotypes: TFE3-associated neurodevelopmental disorder, Intellectual disability, Epilepsy, Coarse facial features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2018 ICOSLG Zornitza Stark Mode of inheritance for gene: ICOSLG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2016 ICOSLG Zornitza Stark reviewed gene: ICOSLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 31532372, 30498080; Phenotypes: Combined immunodeficiency, recurrent bacterial and viral infections, neutropaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2016 TCF20 Chern Lim reviewed gene: TCF20: Rating: GREEN; Mode of pathogenicity: None; Publications: 30739909, 30819258, 25228304; Phenotypes: Developmental delay with variable intellectual impairment and behavioral abnormalities, AD, MIM#618430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2016 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.2014 IL6ST Zornitza Stark Mode of inheritance for gene: IL6ST was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2013 IL6ST Zornitza Stark changed review comment from: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list; to: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed.
Sources: Expert list
Mendeliome v0.2013 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed publications: 28747427, 30309848, 12370259, 16041381, 31914175, 32207811; Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2013 TBX19 Kristin Rigbye reviewed gene: TBX19: Rating: GREEN; Mode of pathogenicity: None; Publications: 15613420, 15613420; Phenotypes: Adrenocorticotropic hormone deficiency, 201400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2013 PIEZO1 Kristin Rigbye reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23695678, 26333996; Phenotypes: Lymphatic malformation 6, 616843, Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.2010 SAMD9L Zornitza Stark Mode of inheritance for gene: SAMD9L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2009 SAMD9L Zornitza Stark reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27259050, 30923096, 30322869; Phenotypes: Ataxia-pancytopenia syndrome, MIM# 159550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2007 RFWD3 Zornitza Stark Mode of inheritance for gene: RFWD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2005 RFWD3 Zornitza Stark reviewed gene: RFWD3: Rating: RED; Mode of pathogenicity: None; Publications: 28691929; Phenotypes: Fanconi anemia, complementation group W, MIM# 617784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2005 MAD2L2 Zornitza Stark gene: MAD2L2 was added
gene: MAD2L2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAD2L2 were set to 27500492
Phenotypes for gene: MAD2L2 were set to Fanconi anemia, complementation group V, MIM# 617243
Review for gene: MAD2L2 was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.2002 UBE2T Zornitza Stark Mode of inheritance for gene: UBE2T was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2000 UBE2T Zornitza Stark reviewed gene: UBE2T: Rating: AMBER; Mode of pathogenicity: None; Publications: 26046368; Phenotypes: Fanconi anemia, complementation group T, MIM# 616435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1999 HAVCR2 Zornitza Stark gene: HAVCR2 was added
gene: HAVCR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HAVCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAVCR2 were set to 30374066; 30792187
Phenotypes for gene: HAVCR2 were set to T-cell lymphoma, subcutaneous panniculitis-like, MIM# 618398
Review for gene: HAVCR2 was set to GREEN
Added comment: Over 20 unrelated individuals reported, note germline confirmation in only a few. Some variants are recurrent: c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met).
Sources: Expert list
Mendeliome v0.1997 TRIM22 Zornitza Stark gene: TRIM22 was added
gene: TRIM22 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRIM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM22 were set to 26836588
Phenotypes for gene: TRIM22 were set to Inflammatory bowel disease
Review for gene: TRIM22 was set to GREEN
Added comment: Three unrelated families reported with bi-allelic variants in this gene, and very early onset IBD, some functional data.
Sources: Expert list
Mendeliome v0.1995 ALPI Zornitza Stark gene: ALPI was added
gene: ALPI was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ALPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALPI were set to 29567797
Phenotypes for gene: ALPI were set to Inflammatory bowel disease
Review for gene: ALPI was set to AMBER
Added comment: Two unrelated individuals, some functional data.
Sources: Expert list
Mendeliome v0.1994 PSMG2 Zornitza Stark gene: PSMG2 was added
gene: PSMG2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PSMG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMG2 were set to 30664889
Phenotypes for gene: PSMG2 were set to CANDLE syndrome; Chronic atypical neutrophilic dermatitis with lipodystrophy
Review for gene: PSMG2 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.1991 NLRP1 Zornitza Stark Mode of inheritance for gene: NLRP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1990 NLRP1 Zornitza Stark reviewed gene: NLRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27965258, 31484767, 27662089; Phenotypes: Autoinflammation with arthritis and dyskeratosis, MIM# 617388, Palmoplantar carcinoma, multiple self-healing 615225, Recurrent respiratory papillomatosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1988 POLA1 Zornitza Stark Mode of inheritance for gene: POLA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1987 POLA1 Zornitza Stark reviewed gene: POLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27019227, 31006512; Phenotypes: Pigmentary disorder, reticulate, with systemic manifestations, X-linked, MIM# 301220, Van Esch-O'Driscoll syndrome OMIM# 301030; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1987 HMOX1 Zornitza Stark reviewed gene: HMOX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21088618, 9884342, 20844238; Phenotypes: Heme oxygenase-1 deficiency, MIM# 614034, Asplenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1987 TIRAP Zornitza Stark edited their review of gene: TIRAP: Changed publications: 28235196; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1987 IRAK1 Zornitza Stark gene: IRAK1 was added
gene: IRAK1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRAK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IRAK1 were set to 28069966
Phenotypes for gene: IRAK1 were set to Susceptibility to bacterial infections
Review for gene: IRAK1 was set to RED
Added comment: Single individual with MECP2 and IRAK1 deletion, died in infancy, immunological phenotype not fully elucidated. In vitro studies.
Sources: Expert list
Mendeliome v0.1985 DBR1 Zornitza Stark gene: DBR1 was added
gene: DBR1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBR1 were set to 29474921
Phenotypes for gene: DBR1 were set to Viral infections of the brainstem
Review for gene: DBR1 was set to GREEN
Added comment: Seven individuals from three unrelated families with viral brainstem encephalitis and bi-allelic hypomorphic variants.
Sources: Expert list
Mendeliome v0.1984 POLR3F Zornitza Stark gene: POLR3F was added
gene: POLR3F was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLR3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3F were set to 30211253
Phenotypes for gene: POLR3F were set to Severe VZV infection
Review for gene: POLR3F was set to RED
Added comment: Missense variant identified in a pair of monozygotic twins. Variant was paternally inherited.
Sources: Expert list
Mendeliome v0.1982 POLR3C Zornitza Stark gene: POLR3C was added
gene: POLR3C was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLR3C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3C were set to 28783042
Phenotypes for gene: POLR3C were set to Severe VZV infection
Review for gene: POLR3C was set to AMBER
Added comment: One individual with POLR3C variant and another individual with both POL3RA and POL3RC variants.
Sources: Expert list
Mendeliome v0.1980 POLR3A Zornitza Stark Mode of inheritance for gene: POLR3A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1979 POLR3A Zornitza Stark reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694, Wiedemann-Rautenstrauch syndrome, MIM# 264090, Susceptibility to severe VZV infection; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1977 IFNAR2 Zornitza Stark Mode of inheritance for gene: IFNAR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1975 IFNAR2 Zornitza Stark reviewed gene: IFNAR2: Rating: RED; Mode of pathogenicity: None; Publications: 26424569; Phenotypes: Immunodeficiency 45, MIM# 616669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1974 IFNAR1 Zornitza Stark gene: IFNAR1 was added
gene: IFNAR1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IFNAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFNAR1 were set to 31270247
Phenotypes for gene: IFNAR1 were set to Severe disease caused by Yellow Fever vaccine and Measles vaccine
Review for gene: IFNAR1 was set to AMBER
Added comment: Two unrelated individuals reported with bi-allelic LoF variants, some functional data.
Sources: Expert list
Mendeliome v0.1972 IRF9 Zornitza Stark gene: IRF9 was added
gene: IRF9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IRF9 were set to 30826365; 30143481
Phenotypes for gene: IRF9 were set to Immunodeficiency 65, susceptibility to viral infections 618648
Review for gene: IRF9 was set to AMBER
Added comment: Two families reported.
Sources: Expert list
Mendeliome v0.1970 CIB1 Zornitza Stark gene: CIB1 was added
gene: CIB1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CIB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIB1 were set to 30068544
Phenotypes for gene: CIB1 were set to Epidermodysplasia verruciformis 3 618267; HPV infections and cancer of the skin
Review for gene: CIB1 was set to GREEN
Added comment: 24 individuals from 6 families reported.
Sources: Expert list
Mendeliome v0.1967 JAK1 Zornitza Stark Mode of inheritance for gene: JAK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1965 JAK1 Zornitza Stark edited their review of gene: JAK1: Changed rating: AMBER; Changed publications: 28111307, 28008925, 30671064; Changed phenotypes: Eosinophilia, Eosinophilic enteritis, Thyroid disease, Poor growth, Viral infections, Susceptibility to mycobacteria and viruses; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1964 SPPL2A Zornitza Stark gene: SPPL2A was added
gene: SPPL2A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SPPL2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPPL2A were set to 30127434
Phenotypes for gene: SPPL2A were set to Susceptibility to mycobacteria and Salmonella
Review for gene: SPPL2A was set to AMBER
Added comment: Three individuals from two unrelated consanguineous family with two different homozygous splice site variants, functional data.
Sources: Expert list
Mendeliome v0.1961 IL23R Zornitza Stark Mode of inheritance for gene: IL23R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1959 IL23R Zornitza Stark reviewed gene: IL23R: Rating: RED; Mode of pathogenicity: None; Publications: 30578351; Phenotypes: Susceptibility to mycobacteria and Salmonella; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1959 IL12RB2 Zornitza Stark gene: IL12RB2 was added
gene: IL12RB2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL12RB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL12RB2 were set to 30578351
Phenotypes for gene: IL12RB2 were set to Susceptibility to mycobacteria and Salmonella
Review for gene: IL12RB2 was set to RED
Added comment: Single individual reported, some functional data.
Sources: Expert list
Mendeliome v0.1957 C17orf62 Zornitza Stark gene: C17orf62 was added
gene: C17orf62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease
Review for gene: C17orf62 was set to GREEN
Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)
Sources: Expert list
Mendeliome v0.1955 MKL1 Zornitza Stark gene: MKL1 was added
gene: MKL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MKL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MKL1 were set to 32128589; 26224645
Phenotypes for gene: MKL1 were set to Neutropaenia with combined immune deficiency
Review for gene: MKL1 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert list
Mendeliome v0.1954 HYOU1 Zornitza Stark gene: HYOU1 was added
gene: HYOU1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HYOU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYOU1 were set to 27913302
Phenotypes for gene: HYOU1 were set to Immunodeficiency 59 and hypoglycemia, MIM# 233600
Review for gene: HYOU1 was set to RED
Added comment: Single individual reported.
Sources: Expert list
Mendeliome v0.1952 SMARCD2 Zornitza Stark gene: SMARCD2 was added
gene: SMARCD2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to 28369036; 28369034
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2, MIM# 617475; Neutropaenia; Neurodevelopmental abnormalities in some; Myelodysplasia
Review for gene: SMARCD2 was set to GREEN
Added comment: Three unrelated families and functional data.
Sources: Expert list
Mendeliome v0.1950 TNFRSF9 Zornitza Stark gene: TNFRSF9 was added
gene: TNFRSF9 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TNFRSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFRSF9 were set to 30872117; 31501153
Phenotypes for gene: TNFRSF9 were set to EBV lymphoproliferation; B-cell lymphoma; Chronic active EBV infection
Review for gene: TNFRSF9 was set to GREEN
Added comment: Six unrelated individuals, two with same homozygous G109S missense variant, functional data.
Sources: Expert list
Mendeliome v0.1947 CTPS1 Zornitza Stark Mode of inheritance for gene: CTPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1946 CTPS1 Zornitza Stark reviewed gene: CTPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24870241; Phenotypes: Immunodeficiency 24, MIM# 615897, Recurrent/chronic bacterial and viral infections (EBV, VZV), EBV lymphoproliferation, B-cell non-Hodgkin lymphoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1946 JAK1 Zornitza Stark gene: JAK1 was added
gene: JAK1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: JAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAK1 were set to 28111307
Phenotypes for gene: JAK1 were set to Eosinophilia; Eosinophilic enteritis; Thyroid disease; Poor growth; Viral infections
Review for gene: JAK1 was set to RED
Added comment: Single family reported (mother and two children) with GoF variant.
Sources: Expert list
Mendeliome v0.1944 IL2RB Zornitza Stark gene: IL2RB was added
gene: IL2RB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL2RB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL2RB were set to 31040184; 31040185
Phenotypes for gene: IL2RB were set to Immunodeficiency 63 with lymphoproliferation and autoimmunity, MIM# 618495; Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune haemolytic anaemia, dermatitis, enteropathy, hypergammaglobulinaemia, recurrent viral (EBV, CMV) infections
Review for gene: IL2RB was set to GREEN
Added comment: Five families reported.
Sources: Expert list
Mendeliome v0.1943 AP3D1 Zornitza Stark gene: AP3D1 was added
gene: AP3D1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AP3D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3D1 were set to 26744459; 9697856
Phenotypes for gene: AP3D1 were set to Hermansky-Pudlak syndrome 10, MIM# 617050; Oculocutaneous albinism; Severe neutropaenia; Recurrent infections; Seizures; Hearing loss; Neurodevelopmental delay
Review for gene: AP3D1 was set to RED
Added comment: Single family and a mouse model.
Sources: Expert list
Mendeliome v0.1942 FAAP24 Zornitza Stark gene: FAAP24 was added
gene: FAAP24 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FAAP24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAAP24 were set to 27473539
Phenotypes for gene: FAAP24 were set to EBV infection-driven lymphoproliferative disease
Review for gene: FAAP24 was set to RED
Added comment: Single sib pair with homozygous missense variant, some functional data.
Sources: Expert list
Mendeliome v0.1941 SH3KBP1 Zornitza Stark gene: SH3KBP1 was added
gene: SH3KBP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SH3KBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH3KBP1 were set to 29636373; 21708930
Phenotypes for gene: SH3KBP1 were set to Immunodeficiency 61, MIM# 300310
Review for gene: SH3KBP1 was set to RED
Added comment: Single family reported, 247.5-kb intragenic deletion detected by array.
Sources: Expert list
Mendeliome v0.1940 ARHGEF1 Zornitza Stark gene: ARHGEF1 was added
gene: ARHGEF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARHGEF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGEF1 were set to 30521495
Phenotypes for gene: ARHGEF1 were set to Immunodeficiency 62, MIM#618459
Review for gene: ARHGEF1 was set to RED
Added comment: Single family, functional data.
Sources: Expert list
Mendeliome v0.1937 ATP6AP1 Zornitza Stark Mode of inheritance for gene: ATP6AP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1936 IRF2BP2 Zornitza Stark gene: IRF2BP2 was added
gene: IRF2BP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IRF2BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BP2 were set to 27016798
Phenotypes for gene: IRF2BP2 were set to Immunodeficiency, common variable, 14, MIM# 617765
Review for gene: IRF2BP2 was set to RED
Added comment: Single family reported only.
Sources: Expert list
Mendeliome v0.1935 TOP2B Zornitza Stark Phenotypes for gene: TOP2B were changed from Autosomal dominant deafness to Autosomal dominant deafness; Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies; Intellectual disability
Mendeliome v0.1933 TOP2B Zornitza Stark changed review comment from: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model.
Sources: Literature; to: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model.
Intellectual disability: two unrelated individuals reported with same de novo variant, c.187C > T, p.(His63Tyr) and also supportive mouse model data.
Sources: Literature
Mendeliome v0.1933 TOP2B Zornitza Stark edited their review of gene: TOP2B: Changed publications: 28343847, 31198993, 31409799, 12773624; Changed phenotypes: Autosomal dominant deafness, Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies, Intellectual disability
Mendeliome v0.1932 TOP2B Zornitza Stark changed review comment from: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Sources: Literature; to: Association with deafness: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Association with immunological phenotypes: Four individuals from three unrelated families reported, all the variants affected the TOPRIM domain, functional data including mouse model.
Sources: Literature
Mendeliome v0.1932 TOP2B Zornitza Stark edited their review of gene: TOP2B: Changed rating: GREEN; Changed publications: 31198993, 31409799, 31953910; Changed phenotypes: Autosomal dominant deafness, Antibody deficiency, recurrent infections, facial dysmorphism, limb anomalies
Mendeliome v0.1931 SLC39A7 Zornitza Stark gene: SLC39A7 was added
gene: SLC39A7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia
Review for gene: SLC39A7 was set to GREEN
Added comment: Five unrelated families with hypomorphic variants and a mouse model recapitulating phenotype.
Sources: Expert list
Mendeliome v0.1929 NFE2L2 Zornitza Stark gene: NFE2L2 was added
gene: NFE2L2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NFE2L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFE2L2 were set to 29018201
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia, MIM# 617744; Recurrent respiratory and skin infection; Growth retardation; Developmental delay, borderline ID; White matter cerebral lesions
Review for gene: NFE2L2 was set to GREEN
Added comment: Four unrelated individuals reported.
Sources: Expert list
Mendeliome v0.1927 ERBIN Zornitza Stark gene: ERBIN was added
gene: ERBIN was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERBIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERBIN were set to 28126831
Phenotypes for gene: ERBIN were set to Recurrent respiratory infections; Susceptibility to S.aureus; Eczema; Hyperextensible joints; Scoliosis; Arterial dilatation in some
Review for gene: ERBIN was set to AMBER
Added comment: Single family and functional data.
Sources: Expert list
Mendeliome v0.1925 ZNF341 Zornitza Stark gene: ZNF341 was added
gene: ZNF341 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZNF341 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF341 were set to 29907691; 29907690
Phenotypes for gene: ZNF341 were set to Hyper-IgE recurrent infection syndrome 3, autosomal recessive, MIM# 618282; Mild facial dysmorphism; Early onset eczema; Recurrent bacterial skin infections, abscesses; Recurrent respiratory infections, lung abscesses and pneumothoraces; Hyperextensible joints, bone fractures, retention of primary teeth
Review for gene: ZNF341 was set to GREEN
Added comment: 19 individuals from 10 families reported, some sharing the same homozygous variants (at least 4 different LoF variants reported).
Sources: Expert list
Mendeliome v0.1923 IL6ST Zornitza Stark gene: IL6ST was added
gene: IL6ST was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175
Phenotypes for gene: IL6ST were set to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.
Review for gene: IL6ST was set to GREEN
Added comment: Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
Sources: Expert list
Mendeliome v0.1920 IL6R Zornitza Stark Mode of inheritance for gene: IL6R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1918 IL6R Zornitza Stark reviewed gene: IL6R: Rating: AMBER; Mode of pathogenicity: None; Publications: 31235509; Phenotypes: Recurrent pyogenic infections, cold abscesses, High circulating IL-6 levels, High IgE; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1917 LIG1 Zornitza Stark gene: LIG1 was added
gene: LIG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG1 were set to 30395541
Phenotypes for gene: LIG1 were set to Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Review for gene: LIG1 was set to GREEN
Added comment: Five individuals from three families.
Sources: Expert list
Mendeliome v0.1916 POLE2 Zornitza Stark gene: POLE2 was added
gene: POLE2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POLE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLE2 were set to 26365386
Phenotypes for gene: POLE2 were set to Combined immunodeficiency; Lymphopaenia; Lack of TRECS, absent proliferation in response to antigens; Hypoglobulinaemia; Recurrent infections, disseminated BCG infections; Autoimmunity; Facial dysmorphism
Review for gene: POLE2 was set to RED
Added comment: Single family reported with homozygous splice site variant.
Sources: Expert list
Mendeliome v0.1914 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis
Review for gene: FCHO1 was set to GREEN
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.
Sources: Expert list
Mendeliome v0.1913 REL Zornitza Stark gene: REL was added
gene: REL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: REL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REL were set to 31103457
Phenotypes for gene: REL were set to Combined immunodeficiency; T cells: normal, decreased memory CD4, poor proliferation; B cells: low, mostly naive, few switched memory B cells, impaired proliferation; Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms; Defective innate immunity
Review for gene: REL was set to RED
Added comment: Single individual from consanguineous family reported with homozygous canonical splice site variant, no functional data.
Sources: Expert list
Mendeliome v0.1912 TFRC Zornitza Stark Phenotypes for gene: TFRC were changed from to Immunodeficiency 46, MIM# 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia
Mendeliome v0.1910 TFRC Zornitza Stark Mode of inheritance for gene: TFRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1908 TFRC Zornitza Stark reviewed gene: TFRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 26642240; Phenotypes: Immunodeficiency 46, MIM# 616740, T cells: normal number, poor proliferation, B cells: normal number, low memory B cells, recurrent infections, neutorpaenia, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1908 TET2 Zornitza Stark changed review comment from: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma.; to: No evidence for Mendelian gene-disease association. Somatic TET2 variants are commonly found in cancers. One Finnish family reported where germline variant present 7 individuals, of whom 3 had lymphoma. Another French family reported with three sibs: frameshift variant and myeloid malignancies. Contribution of germline variants to malignancy risk to be established.
Mendeliome v0.1907 RELA Zornitza Stark gene: RELA was added
gene: RELA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RELA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RELA were set to 28600438; 29305315
Phenotypes for gene: RELA were set to Mucocutaneous ulceration, chronic, MIM# 618287; Impaired NFkB activation; reduced production of inflammatory cytokines; autoimmune cytopaenias
Review for gene: RELA was set to AMBER
Added comment: Two families reported, somewhat different phenotypes.
Sources: Expert list
Mendeliome v0.1905 RELB Zornitza Stark gene: RELB was added
gene: RELB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RELB were set to 7834753; 26385063
Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections
Review for gene: RELB was set to AMBER
Added comment: Single family reported, functional data.
Sources: Expert list
Mendeliome v0.1904 CD247 Zornitza Stark Phenotypes for gene: CD247 were changed from to Immunodeficiency 25, MIM# 610163; Absent T cells; Normal B cells; Normal NK cells
Mendeliome v0.1902 CD247 Zornitza Stark Mode of inheritance for gene: CD247 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1901 CD247 Zornitza Stark reviewed gene: CD247: Rating: RED; Mode of pathogenicity: None; Publications: 16672702; Phenotypes: Immunodeficiency 25, MIM# 610163, Absent T cells, Normal B cells, Normal NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1900 NSMCE2 Tiong Tan gene: NSMCE2 was added
gene: NSMCE2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSMCE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSMCE2 were set to 25105364
Phenotypes for gene: NSMCE2 were set to SECKEL SYNDROME 10
Penetrance for gene: NSMCE2 were set to Complete
Review for gene: NSMCE2 was set to AMBER
Added comment: Biallelic hypomorphic variants in two unrelated women with microcephalic primordial dwarfism, insulin-resistant diabetes, fatty liver, and hypertriglyceridemia developing in childhood; and primary gonadal failure. Good quality functional evidence. No additional confirmatory cases since 2014 publication
Sources: Literature
Mendeliome v0.1898 PLEKHA5 Zornitza Stark reviewed gene: PLEKHA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 29805042; Phenotypes: cleft lip, cleft palate; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1897 TRPA1 Zornitza Stark gene: TRPA1 was added
gene: TRPA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TRPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPA1 were set to 20547126; 16564016; 21468319; 28314413; 24778270; 24564660; 20718100
Phenotypes for gene: TRPA1 were set to Episodic pain syndrome, familial, 1, MIM# 615040
Review for gene: TRPA1 was set to AMBER
Added comment: Single family and a lot of functional data.
Sources: Expert list
Mendeliome v0.1896 PLEKHA5 Tiong Tan gene: PLEKHA5 was added
gene: PLEKHA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA5 were set to 29805042
Phenotypes for gene: PLEKHA5 were set to cleft lip; cleft palate
Penetrance for gene: PLEKHA5 were set to Complete
Review for gene: PLEKHA5 was set to GREEN
Added comment: Sources: Literature
Mendeliome v0.1894 CNKSR1 Zornitza Stark gene: CNKSR1 was added
gene: CNKSR1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CNKSR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNKSR1 were set to 30450701; 30237576; 21937992
Phenotypes for gene: CNKSR1 were set to Intellectual disability
Review for gene: CNKSR1 was set to AMBER
Added comment: Three families reported, two as part of large cohorts reporting multiple novel genes. Note the family reported in PMID 30450701 appears to be the same family as reported in PMID 21937992. Some functional data in PMID 30450701, including Drosophila model.
Sources: Expert Review
Mendeliome v0.1892 FRMD4A Zornitza Stark gene: FRMD4A was added
gene: FRMD4A was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005; 30214071
Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Review for gene: FRMD4A was set to AMBER
Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant.
Sources: Expert Review
Mendeliome v0.1890 NEK10 Zornitza Stark gene: NEK10 was added
gene: NEK10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NEK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEK10 were set to 31959991
Phenotypes for gene: NEK10 were set to Primary ciliary dyskinesia; bronchiectasis
Review for gene: NEK10 was set to GREEN
Added comment: Nine individuals from 5 unrelated families, some functional data.
Sources: NHS GMS
Mendeliome v0.1888 PIGK Zornitza Stark gene: PIGK was added
gene: PIGK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGK were set to 32220290
Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy
Review for gene: PIGK was set to GREEN
Added comment: 12 individuals from 9 unrelated families reported.
Sources: Literature
Mendeliome v0.1886 ADARB1 Zornitza Stark gene: ADARB1 was added
gene: ADARB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADARB1 were set to 32220291
Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures
Review for gene: ADARB1 was set to GREEN
Added comment: Four unrelated individuals with bi-allelic variants in this gene.
Sources: Literature
Mendeliome v0.1883 HSPB3 Zornitza Stark Mode of inheritance for gene: HSPB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1881 HSPB3 Zornitza Stark reviewed gene: HSPB3: Rating: RED; Mode of pathogenicity: None; Publications: 20142617, 27549087; Phenotypes: Neuronopathy, distal hereditary motor, type IIC, MIM# 613376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1879 FBXO38 Zornitza Stark Mode of inheritance for gene: FBXO38 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1877 FBXO38 Zornitza Stark reviewed gene: FBXO38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24207122, 31420593; Phenotypes: Neuronopathy, distal hereditary motor, type IID, 615575, dHMN/dSMA; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1876 DRP2 Zornitza Stark gene: DRP2 was added
gene: DRP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DRP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: DRP2 were set to 26227883; 11430802; 31217940; 22764250; 29473052
Phenotypes for gene: DRP2 were set to Charcot Marie Tooth, intermediate X-linked; HMSN
Review for gene: DRP2 was set to GREEN
Added comment: Three unrelated families, functional data.
Sources: Expert list
Mendeliome v0.1874 DGAT2 Zornitza Stark gene: DGAT2 was added
gene: DGAT2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DGAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGAT2 were set to 26786738
Phenotypes for gene: DGAT2 were set to axonal Charcot-Marie-Tooth disease
Review for gene: DGAT2 was set to AMBER
Added comment: Single family (father and son) reported, with supporting in vitro functional assays and a zebrafish model.
Sources: Expert Review
Mendeliome v0.1872 ERLIN1 Bryony Thompson gene: ERLIN1 was added
gene: ERLIN1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ERLIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERLIN1 were set to 24482476
Phenotypes for gene: ERLIN1 were set to Spastic paraplegia 62 MIM#615681
Review for gene: ERLIN1 was set to GREEN
Added comment: Three unrelated consanguineous families with early onset pure HSP.
Sources: Expert list
Mendeliome v0.1866 ARID2 Zornitza Stark Mode of inheritance for gene: ARID2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1865 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to Charcot-Marie-Tooth disease, axonal, type 20; Mental retardation, autosomal dominant 13; Spinal muscular atrophy, lower extremity-predominant 1
Mendeliome v0.1862 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1858 PQBP1 Zornitza Stark Mode of inheritance for gene: PQBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1854 CHD3 Zornitza Stark Mode of inheritance for gene: CHD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1851 DLG3 Zornitza Stark Mode of inheritance for gene: DLG3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1847 FBN2 Zornitza Stark Mode of inheritance for gene: FBN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1845 AGTPBP1 Zornitza Stark gene: AGTPBP1 was added
gene: AGTPBP1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six.
Sources: NHS GMS
Mendeliome v0.1842 ADGRG6 Zornitza Stark edited their review of gene: ADGRG6: Added comment: Three families reported originally with severe prenatal-onset arthrogryposis (PMID: 26004201), one family with more complex neurological phenotype (PMID:30549416).; Changed rating: GREEN; Changed publications: 30549416, 26004201; Changed phenotypes: Lethal congenital contracture syndrome 9, OMIM #616503; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1842 ARID2 Elena Savva reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30838730; Phenotypes: Coffin-Siris syndrome 6; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1842 DYNC1H1 Elena Savva reviewed gene: DYNC1H1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25512093, 28196890; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 20, Mental retardation, autosomal dominant 13, Spinal muscular atrophy, lower extremity-predominant 1; Mode of inheritance: None
Mendeliome v0.1842 PQBP1 Elena Savva reviewed gene: PQBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:31840929, 14634649, 20410308; Phenotypes: Renpenning syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.1842 CHD3 Elena Savva reviewed gene: CHD3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:30397230; Phenotypes: Snijders Blok-Campeau syndrome (618205); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1842 DLG3 Elena Savva reviewed gene: DLG3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 28777483; Phenotypes: Mental retardation, X-linked 90; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1842 FBN2 Elena Savva reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 19473076, 11068201; Phenotypes: Contractural arachnodactyly, congenital 121050, Macular degeneration, early-onset 616118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1841 EIF2AK2 Zornitza Stark gene: EIF2AK2 was added
gene: EIF2AK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 32197074
Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness
Review for gene: EIF2AK2 was set to GREEN
Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype.
Sources: Literature
Mendeliome v0.1840 EIF2AK1 Zornitza Stark gene: EIF2AK1 was added
gene: EIF2AK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK1 were set to 32197074
Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities
Review for gene: EIF2AK1 was set to RED
Added comment: Single individual reported with de novo variant in this gene.
Sources: Literature
Mendeliome v0.1838 NOVA2 Zornitza Stark gene: NOVA2 was added
gene: NOVA2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOVA2 were set to 32197073
Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia
Mode of pathogenicity for gene: NOVA2 was set to Other
Review for gene: NOVA2 was set to GREEN
Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism.
Sources: Literature
Mendeliome v0.1836 GNB2 Sue White gene: GNB2 was added
gene: GNB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 31698099
Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features
Penetrance for gene: GNB2 were set to Complete
Review for gene: GNB2 was set to AMBER
Added comment: single report of patient with de novo missense variant in GNB2 and intellectual disability. Emerging evidence of other de no missense variants in GNB2 and ID
Sources: Literature
Mendeliome v0.1834 NRROS Sue White gene: NRROS was added
gene: NRROS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRROS were set to 32100099; 32197075
Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy
Penetrance for gene: NRROS were set to Complete
Review for gene: NRROS was set to GREEN
Added comment: normal development or mild developmental delay until onset of regression around age of 1 concurrent with epilepsy
biallelic LOF mutations with functional evidence of pathogenicity
Sources: Literature
Mendeliome v0.1831 CNOT3 Zornitza Stark Mode of inheritance for gene: CNOT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1830 CNOT3 Zornitza Stark reviewed gene: CNOT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31201375; Phenotypes: Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, MIM# 618672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1828 CBS Zornitza Stark Mode of inheritance for gene: CBS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1827 CBS Kristin Rigbye reviewed gene: CBS: Rating: GREEN; Mode of pathogenicity: None; Publications: 7506602, 10338090; Phenotypes: Homocystinuria, B6-responsive and nonresponsive types, 236200, Thrombosis, hyperhomocysteinemic, 236200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1823 SLC25A21 Zornitza Stark gene: SLC25A21 was added
gene: SLC25A21 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A21 were set to 29517768
Phenotypes for gene: SLC25A21 were set to Mitochondrial DNA depletion syndrome-18, MIM#618811
Review for gene: SLC25A21 was set to AMBER
Added comment: One case with a homozygous variant and functional assays showing mitochondrial dysfunction.
Sources: NHS GMS
Mendeliome v0.1821 SLC25A10 Zornitza Stark gene: SLC25A10 was added
gene: SLC25A10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A10 were set to 29211846
Phenotypes for gene: SLC25A10 were set to Intractable epileptic encephalopathy
Review for gene: SLC25A10 was set to AMBER
Added comment: One case with intractable epileptic encephalopathy with complex I deficiency, with biallelic variants. Yeast SLC25A10 ortholog lack-of-function causes impairment in mitochondrial respiration, reduced mtDNA copy number and oxidative stress vulnerability.
Sources: NHS GMS
Mendeliome v0.1817 QARS Zornitza Stark Mode of inheritance for gene: QARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1816 QARS Zornitza Stark reviewed gene: QARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28620870, 25471517, 25432320, 25041233, 24656866, 32042906; Phenotypes: Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1815 PTCD3 Zornitza Stark gene: PTCD3 was added
gene: PTCD3 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 19427859
Phenotypes for gene: PTCD3 were set to Intellectual disability; optic atrophy; Leigh-like syndrome
Review for gene: PTCD3 was set to AMBER
Added comment: One compound heterozygote case and functional assays. Essential subunit of oxidative phosphorylation (OXPHOS) complexes.
Sources: NHS GMS
Mendeliome v0.1814 PTCD1 Zornitza Stark gene: PTCD1 was added
gene: PTCD1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: PTCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD1 were set to 25058219
Phenotypes for gene: PTCD1 were set to Cardiomyopathy
Review for gene: PTCD1 was set to RED
Added comment: Single case reported with no functional characterisation. Biochemical analyses of heart tissue identified global COX defect. No OMIM phenotype.
Sources: NHS GMS
Mendeliome v0.1812 PNPLA4 Zornitza Stark Mode of inheritance for gene: PNPLA4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1809 OXA1L Zornitza Stark gene: OXA1L was added
gene: OXA1L was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: OXA1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXA1L were set to 30201738; 16435202
Phenotypes for gene: OXA1L were set to Encephalopathy; hypotonia; developmental delay
Review for gene: OXA1L was set to AMBER
Added comment: Single family reported with biochemical and molecular analyses of patient skeletal muscle and fibroblasts. In vitro functional assays in human cell lines, Drosophila model, and yeast-based assays. Loss of function affects oxidative phosphorylation complexes IV and V.
Sources: NHS GMS
Mendeliome v0.1807 NSUN3 Zornitza Stark gene: NSUN3 was added
gene: NSUN3 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN3 were set to 27356879
Phenotypes for gene: NSUN3 were set to combined mitochondrial respiratory chain complex deficiency
Review for gene: NSUN3 was set to AMBER
Added comment: A single compound heterozygous case. Patient-derived fibroblasts exhibited severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. In vitro functional assays also conducted.
Sources: NHS GMS
Mendeliome v0.1805 NDUFB10 Zornitza Stark gene: NDUFB10 was added
gene: NDUFB10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFB10 were set to 28040730; 32025618
Phenotypes for gene: NDUFB10 were set to fatal infantile lactic acidosis; cardiomyopathy
Review for gene: NDUFB10 was set to AMBER
Added comment: Single compound heterozygote case and mitochondrial phenotype. Assays of respiratory chain enzyme activities and functions in patient tissues/fibroblasts and in vitro functional assays. Plant model system supporting mitochondrial complex I dysfunction.
Sources: NHS GMS
Mendeliome v0.1801 MRM2 Zornitza Stark gene: MRM2 was added
gene: MRM2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRM2 were set to 28973171
Phenotypes for gene: MRM2 were set to MELAS-like
Review for gene: MRM2 was set to AMBER
Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA.
Sources: NHS GMS
Mendeliome v0.1799 MRPL3 Zornitza Stark changed review comment from: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies.; to: 1 French family with 4 sibs with severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, some functional studies. 1 male infant with a severe mitochondrial disorder - compound heterozygous mutations in the MRPL3 gene, no functional studies.
Mendeliome v0.1798 IDH3A Zornitza Stark gene: IDH3A was added
gene: IDH3A was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: IDH3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDH3A were set to 31012789; 30478029; 30058936; 28412069
Phenotypes for gene: IDH3A were set to Retinitis pigmentosa
Review for gene: IDH3A was set to GREEN
Added comment: Six unrelated families reported with retinitis pigmentosa. Mouse model.
Sources: NHS GMS
Mendeliome v0.1797 GATC Zornitza Stark gene: GATC was added
gene: GATC was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: GATC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATC were set to 30283131
Phenotypes for gene: GATC were set to Mitochondrial cardiomyopathy
Review for gene: GATC was set to RED
Added comment: Two families with 6 affected individuals reported; same homozygous variant.
Sources: NHS GMS
Mendeliome v0.1796 GATB Zornitza Stark gene: GATB was added
gene: GATB was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: GATB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GATB were set to 30283131
Phenotypes for gene: GATB were set to Mitochondrial cardiomyopathy
Review for gene: GATB was set to RED
Added comment: Single family reported with two affected siblings
Sources: NHS GMS
Mendeliome v0.1795 EFTUD2 Elena Savva reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type 610536; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1795 PAX1 Elena Savva reviewed gene: PAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29681087, 28657137, 23851939; Phenotypes: ?Otofaciocervical syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1795 SHANK2 Elena Savva reviewed gene: SHANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30072871, 30911184; Phenotypes: {Autism susceptibility 17}, Autism spectrum disorder with or without intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1795 IFT172 Elena Savva reviewed gene: IFT172: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26763875; Phenotypes: Retinitis pigmentosa 71 616394, Short-rib thoracic dysplasia 10 with or without polydactyly - 615630, Bardet-Biedl syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1793 FECH Zornitza Stark Mode of inheritance for gene: FECH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1790 ADAM17 Zornitza Stark Mode of inheritance for gene: ADAM17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1788 ZNF462 Zornitza Stark Added comment: Comment when marking as ready: Multiple congenital anomaly syndrome characterised by variable but usually mild global developmental delay and common craniofacial abnormalities, including ptosis, abnormal head shape, downslanting palpebral fissures, epicanthal folds, arched eyebrows, and short upturned nose. Many patients have hypotonia and feeding difficulties. A few patients show agenesis of the corpus callosum on brain imaging. Most cases occur sporadically, but there are rare familial cases that show highly variable expressivity in the phenotypic manifestations.
Mendeliome v0.1785 ZNF462 Zornitza Stark Mode of inheritance for gene: ZNF462 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1784 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from to Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ) 309541
Mendeliome v0.1782 HCFC1 Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1781 TFAM Zornitza Stark gene: TFAM was added
gene: TFAM was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156
Review for gene: TFAM was set to AMBER
Added comment: One consanguineous family segregates a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation.
Sources: NHS GMS
Mendeliome v0.1779 TIMM22 Zornitza Stark gene: TIMM22 was added
gene: TIMM22 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TIMM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMM22 were set to 30452684
Phenotypes for gene: TIMM22 were set to mitochondrial myopathy; hypotonia; gastroesophageal reflux disease
Review for gene: TIMM22 was set to AMBER
Added comment: One compound heterozygote case identified with supporting in vitro and patient cell functional assays.
Sources: NHS GMS
Mendeliome v0.1777 TIMMDC1 Zornitza Stark gene: TIMMDC1 was added
gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMMDC1 were set to 28604674; 30981218
Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251
Review for gene: TIMMDC1 was set to AMBER
Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect.
Sources: NHS GMS
Mendeliome v0.1775 TMEM65 Zornitza Stark gene: TMEM65 was added
gene: TMEM65 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM65 were set to 28295037
Phenotypes for gene: TMEM65 were set to Mitochondrial encephalomyopathy
Review for gene: TMEM65 was set to AMBER
Added comment: One homozygous case with a mitochondrial encephalomyopathy and functional assays showing the protein is important for mitochondrial respiration and mtDNA copy number maintenance.
Sources: NHS GMS
Mendeliome v0.1774 FECH Michelle Torres reviewed gene: FECH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20105171, 23016163; Phenotypes: Protoporphyria, erythropoietic, 1 177000 AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1774 ADAM17 Lauren Akesson reviewed gene: ADAM17: Rating: AMBER; Mode of pathogenicity: None; Publications: 22010916, 25804906, 21041656, 22236242; Phenotypes: Inflammatory neonatal-onset skin and bowel disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1773 SSBP1 Bryony Thompson gene: SSBP1 was added
gene: SSBP1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SSBP1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SSBP1 were set to 31298765; 31479473; 31550237; 31550240
Phenotypes for gene: SSBP1 were set to Optic atrophy with or without extraocular phenotypes
Review for gene: SSBP1 was set to GREEN
Added comment: At least 9 dominant families/cases and 1 recessive with optic atrophy with/without additional clinical features, including retinal macular dystrophy, sensorineural deafness, mitochondrial myopathy, and kidney failure. Supporting evidence in functional assays and zebrafish model.
Sources: NHS GMS
Mendeliome v0.1772 ZNF462 Elena Savva reviewed gene: ZNF462: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28513610; Phenotypes: Weiss-Kruszka syndrome, 618619; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1772 HCFC1 Elena Savva reviewed gene: HCFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23000143; Phenotypes: Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ) 309541; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1771 COX6A2 Zornitza Stark gene: COX6A2 was added
gene: COX6A2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COX6A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX6A2 were set to 31155743; 23460811
Phenotypes for gene: COX6A2 were set to Mitochondrial complex IV deficiency, MIM# 220110
Review for gene: COX6A2 was set to GREEN
Added comment: Two unrelated families and two mouse models.
Sources: Expert list
Mendeliome v0.1769 YME1L1 Zornitza Stark gene: YME1L1 was added
gene: YME1L1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YME1L1 were set to 30544562; 27495975
Phenotypes for gene: YME1L1 were set to Optic atrophy 11, MIM#617302
Review for gene: YME1L1 was set to AMBER
Added comment: One consanguineous family with a homozygous variant and functional assays. YME1L leads to mitochondrial fragmentation and severely disorganized and attenuated cristae architecture in in vitro functional assays.
Sources: NHS GMS
Mendeliome v0.1766 ANXA11 Bryony Thompson gene: ANXA11 was added
gene: ANXA11 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ANXA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANXA11 were set to 28469040; 29845112; 30109997
Phenotypes for gene: ANXA11 were set to Amytrophic lateral sclerosis 23 MIM#617839
Review for gene: ANXA11 was set to GREEN
Added comment: 4 different missense variants in 10 patients from 7 unrelated families with amyotrophic lateral sclerosis and functional assays supporting association.
Sources: Expert list
Mendeliome v0.1763 UQCRQ Zornitza Stark Mode of inheritance for gene: UQCRQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1761 UQCRQ Zornitza Stark reviewed gene: UQCRQ: Rating: AMBER; Mode of pathogenicity: None; Publications: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4, MIM# 615159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1759 UQCRC2 Zornitza Stark Mode of inheritance for gene: UQCRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1757 UQCRC2 Zornitza Stark reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1755 UQCC3 Zornitza Stark Mode of inheritance for gene: UQCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1753 UQCC3 Zornitza Stark reviewed gene: UQCC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25008109, 28804536; Phenotypes: Mitochondrial complex III deficiency, nuclear type 9, MIM# 616111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1751 TXN2 Zornitza Stark Mode of inheritance for gene: TXN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1749 TXN2 Zornitza Stark reviewed gene: TXN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26626369, 12529397; Phenotypes: Combined oxidative phosphorylation deficiency 29, MIM# 616811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1747 TARS2 Zornitza Stark Mode of inheritance for gene: TARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1745 TARS2 Zornitza Stark reviewed gene: TARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24827421, 26811336; Phenotypes: Combined oxidative phosphorylation deficiency 21, MIM# 615918; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1744 SLC25A32 Zornitza Stark gene: SLC25A32 was added
gene: SLC25A32 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive, MIM# 616839
Review for gene: SLC25A32 was set to GREEN
Added comment: Two unrelated families reported with functional data. Muscle biopsy showed ragged-red fibers and lipid storage mainly in type I oxidative fibers, small type II fibers, and poor immunostaining for succinate dehydrogenase (FAD-dependent mitochondrial respiratory chain complex II). Oral supplementation with riboflavin led to dramatic improvement in the clinical and biologic abnormalities.
Sources: Expert list
Mendeliome v0.1741 NFS1 Zornitza Stark Mode of inheritance for gene: NFS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1739 NFS1 Zornitza Stark reviewed gene: NFS1: Rating: RED; Mode of pathogenicity: None; Publications: 24498631; Phenotypes: Complex II/III deficiency, multisystem organ failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1737 NDUFA6 Zornitza Stark Mode of inheritance for gene: NDUFA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1736 NDUFA6 Zornitza Stark reviewed gene: NDUFA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30245030; Phenotypes: Mitochondrial complex I deficiency, nuclear type 33, MIM# 618253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1734 NDUFA4 Zornitza Stark Mode of inheritance for gene: NDUFA4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1732 NDUFA4 Zornitza Stark reviewed gene: NDUFA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 30361421, 28988874, 23746447; Phenotypes: Leigh syndrome, Complex IV deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1730 NDUFA13 Zornitza Stark Mode of inheritance for gene: NDUFA13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1728 NDUFA13 Zornitza Stark reviewed gene: NDUFA13: Rating: RED; Mode of pathogenicity: None; Publications: 25901006; Phenotypes: Mitochondrial complex I deficiency, nuclear type 28, MIM# 618249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1727 NADK2 Zornitza Stark gene: NADK2 was added
gene: NADK2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NADK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADK2 were set to 24847004; 29388319; 27940755
Phenotypes for gene: NADK2 were set to 2,4-dienoyl-CoA reductase deficiency, MIM# 616034
Review for gene: NADK2 was set to GREEN
gene: NADK2 was marked as current diagnostic
Added comment: Mitochondrial dysfunction resulting in severe neurologic and metabolic dysfunction beginning in early infancy reported in two individuals with confirmed variants in this gene. Another individual with homozygous hypomorphic start loss variant g.36241900 A>G p. Met1Val and milder phenotype reported (PMID:29388319).
Sources: Expert list
Mendeliome v0.1725 ISCA1 Zornitza Stark gene: ISCA1 was added
gene: ISCA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122
Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613
Review for gene: ISCA1 was set to GREEN
gene: ISCA1 was marked as current diagnostic
Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families.
Sources: Expert list
Mendeliome v0.1722 ERCC5 Zornitza Stark Mode of inheritance for gene: ERCC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1719 BTD Zornitza Stark Mode of inheritance for gene: BTD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1715 CTNNB1 Zornitza Stark Mode of inheritance for gene: CTNNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1714 CTNNB1 Zornitza Stark reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25326669, 29435196, 27915094, 30640974; Phenotypes: Exudative vitreoretinopathy 7, MIM# 617572, Neurodevelopmental disorder with spastic diplegia and visual defects, MIM# 615075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1714 ERCC5 Chern Lim reviewed gene: ERCC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30838033, 24700531; Phenotypes: Cerebrooculofacioskeletal syndrome 3, MIM# 616570, Xeroderma pigmentosum, group G, MIM# 278780, Xeroderma pigmentosum, group G/Cockayne syndrome, MIM# 278780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1714 BTD Chern Lim reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: None; Publications: 10801053, 12359137; Phenotypes: Biotinidase deficiency, MIM 253260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1714 CTNNB1 Teresa Zhao reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: PMID: 29435196, PMID: 27915094, PMID: 30640974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1713 ARL11 Zornitza Stark Mode of inheritance for gene: ARL11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1711 ARL11 Zornitza Stark reviewed gene: ARL11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1709 CLCN6 Zornitza Stark Mode of inheritance for gene: CLCN6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1707 CLCN6 Zornitza Stark reviewed gene: CLCN6: Rating: RED; Mode of pathogenicity: None; Publications: 25794116, 21107136; Phenotypes: Benign partial epilepsy, febrile seizures, NCL; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1706 SEMA6B Zornitza Stark gene: SEMA6B was added
gene: SEMA6B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA6B were set to 32169168
Phenotypes for gene: SEMA6B were set to Progressive myoclonic epilepsy
Mode of pathogenicity for gene: SEMA6B was set to Other
Review for gene: SEMA6B was set to GREEN
Added comment: Five individuals from unrelated families reported with de novo variants in the last exon, escaping NMD.
Sources: Literature
Mendeliome v0.1701 CAMTA1 Zornitza Stark Mode of inheritance for gene: CAMTA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1700 CAMTA1 Zornitza Stark reviewed gene: CAMTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32157189, 22693284; Phenotypes: Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1699 TNNI3K Zornitza Stark gene: TNNI3K was added
gene: TNNI3K was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TNNI3K was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI3K were set to 30010057; 29355681
Phenotypes for gene: TNNI3K were set to Cardiac conduction disease with or without dilated cardiomyopathy, MIM# 616117
Review for gene: TNNI3K was set to GREEN
gene: TNNI3K was marked as current diagnostic
Added comment: At least 6 multigenerational families reported where variants segregated with disease.
Sources: Expert list
Mendeliome v0.1698 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from to Mental retardation, autosomal recessive 49, MIM#616281
Mendeliome v0.1696 GPT2 Zornitza Stark Mode of inheritance for gene: GPT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1695 GPT2 Zornitza Stark reviewed gene: GPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27601654, 25758935; Phenotypes: Mental retardation, autosomal recessive 49, MIM#616281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1693 ERCC6L2 Zornitza Stark Mode of inheritance for gene: ERCC6L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1692 ERCC6L2 Zornitza Stark reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24507776, 27185855; Phenotypes: Bone marrow failure syndrome 2, MIM# 615715; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1690 SUPT16H Zornitza Stark gene: SUPT16H was added
gene: SUPT16H was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SUPT16H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT16H were set to 31924697
Phenotypes for gene: SUPT16H were set to Intellectual disability; Abnormality of the corpus callosum
Review for gene: SUPT16H was set to GREEN
Added comment: Four unrelated individuals with de novo missense variants in this gene. Publication also reports on a deletion, but note this includes other genes and the individual also had another CNV.
Sources: Literature
Mendeliome v0.1687 RARS Zornitza Stark Mode of inheritance for gene: RARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1686 RARS Zornitza Stark reviewed gene: RARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31814314; Phenotypes: Leukodystrophy, hypomyelinating, 9 MIM# 616140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1684 TNR Zornitza Stark gene: TNR was added
gene: TNR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNR were set to 32099069
Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Review for gene: TNR was set to GREEN
Added comment: 13 individuals from 8 unrelated families reported.
Sources: Literature
Mendeliome v0.1681 RSPRY1 Zornitza Stark Mode of inheritance for gene: RSPRY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1679 RSPRY1 Zornitza Stark reviewed gene: RSPRY1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26365341; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1677 RPS23 Zornitza Stark Mode of inheritance for gene: RPS23 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1676 RPS23 Zornitza Stark Mode of inheritance for gene: RPS23 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1674 RPS23 Zornitza Stark reviewed gene: RPS23: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257692; Phenotypes: Brachycephaly, trichomegaly, and developmental delay, MIM# 617412; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1667 HMGA2 Zornitza Stark Mode of inheritance for gene: HMGA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1665 HMGA2 Zornitza Stark reviewed gene: HMGA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 29655892, 25809938; Phenotypes: Silver-Russel syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1663 MFSD2A Zornitza Stark Phenotypes for gene: MFSD2A were changed from to Microcephaly 15, primary, autosomal recessive, MIM# 616486
Mendeliome v0.1661 MFSD2A Zornitza Stark Mode of inheritance for gene: MFSD2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1660 MFSD2A Zornitza Stark reviewed gene: MFSD2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005865, 26005868, 24828044; Phenotypes: Microcephaly 15, primary, autosomal recessive, MIM# 616486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1659 MED12L Zornitza Stark gene: MED12L was added
gene: MED12L was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED12L were set to 31155615
Phenotypes for gene: MED12L were set to Intellectual disability; Seizures; Autism
Review for gene: MED12L was set to GREEN
Added comment: 7 individuals reported, 3 with CNVs (encompassing other genes) and 4 with SNVs (frameshift, nonsense and splice site).
Sources: Expert list
Mendeliome v0.1657 MCM3AP Zornitza Stark gene: MCM3AP was added
gene: MCM3AP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124
Review for gene: MCM3AP was set to GREEN
gene: MCM3AP was marked as current diagnostic
Added comment: At least 10 families reported.
Sources: Expert list
Mendeliome v0.1654 MAPRE2 Zornitza Stark Mode of inheritance for gene: MAPRE2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1653 MAPRE2 Zornitza Stark reviewed gene: MAPRE2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26637975; Phenotypes: Symmetric circumferential skin creases, congenital, 2, MIM# 616734; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1653 PURA Zornitza Stark Phenotypes for gene: PURA were changed from to Mental retardation, autosomal dominant 31, MIM# 616158
Mendeliome v0.1651 PURA Zornitza Stark Mode of inheritance for gene: PURA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1650 PURA Zornitza Stark reviewed gene: PURA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439098, 25342064, 12972605; Phenotypes: Mental retardation, autosomal dominant 31, MIM# 616158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1650 BPTF Zornitza Stark Phenotypes for gene: BPTF were changed from to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD, MIM#617755
Mendeliome v0.1648 BPTF Zornitza Stark Mode of inheritance for gene: BPTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1647 TRIO Zornitza Stark Phenotypes for gene: TRIO were changed from to Mental retardation, autosomal dominant 44, MIM# 617061
Mendeliome v0.1645 TRIO Zornitza Stark Mode of inheritance for gene: TRIO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1644 TRIO Zornitza Stark reviewed gene: TRIO: Rating: GREEN; Mode of pathogenicity: None; Publications: 26721934, 32109419; Phenotypes: Mental retardation, autosomal dominant 44, MIM# 617061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1644 MAN1B1 Zornitza Stark Phenotypes for gene: MAN1B1 were changed from to Mental retardation, autosomal recessive 15, MIM#614202
Mendeliome v0.1642 MAN1B1 Zornitza Stark Mode of inheritance for gene: MAN1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1640 KMT2C Zornitza Stark Mode of inheritance for gene: KMT2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1638 GLRX5 Zornitza Stark Mode of inheritance for gene: GLRX5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1636 NUDT2 Zornitza Stark gene: NUDT2 was added
gene: NUDT2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600
Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability
Review for gene: NUDT2 was set to AMBER
Added comment: 7 affected individuals from 4 Saudi families, with same homozygous truncating variant.
Sources: Expert list
Mendeliome v0.1635 BPTF Michelle Torres reviewed gene: BPTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942966; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1635 SLC26A4 Elena Savva reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24599119; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1635 MAP3K7 Michelle Torres reviewed gene: MAP3K7: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27426734, 27426733; Phenotypes: Cardiospondylocarpofacial syndrome 157800 AD, Frontometaphyseal dysplasia 2 617137 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1635 MAN1B1 Elena Savva reviewed gene: MAN1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24348268; Phenotypes: Mental retardation, autosomal recessive 15; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1635 KMT2C Elena Savva reviewed gene: KMT2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kleefstra syndrome 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1635 GLRX5 Elena Savva reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Anemia, sideroblastic, 3, pyridoxine-refractory, Spasticity, childhood-onset, with hyperglycinemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1634 NKAP Zornitza Stark gene: NKAP was added
gene: NKAP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NKAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NKAP were set to 26358559; 26350204; 31587868
Phenotypes for gene: NKAP were set to Intellectual disability
Review for gene: NKAP was set to GREEN
gene: NKAP was marked as current diagnostic
Added comment: 10 males from 8 unrelated families with missense mutations in NKAP (on Xq24) Hypotonia and tall stature with Marfanoid habitus was predominant phenotype. One variant (NM_024528:c.988G>A / p.Arg333Gln)
Sources: Expert list
Mendeliome v0.1631 TBR1 Zornitza Stark Mode of inheritance for gene: TBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1628 GNRHR Zornitza Stark Mode of inheritance for gene: GNRHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1627 GNRHR Kristin Rigbye reviewed gene: GNRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 28348023, 9371856; Phenotypes: Hypogonadotropic hypogonadism 7 without anosmia, 146110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1627 TBR1 Melanie Marty reviewed gene: TBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25232744, 30250039; Phenotypes: Intellectual developmental disorder with autism and speech delay 606053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1625 MYO9A Zornitza Stark Mode of inheritance for gene: MYO9A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1624 MYO9A Zornitza Stark reviewed gene: MYO9A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26752647, 27259756; Phenotypes: Congenital myasthenic syndrome 24, presynaptic, MIM# 618198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1623 ZDHHC15 Zornitza Stark Mode of inheritance for gene: ZDHHC15 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1621 ZDHHC15 Zornitza Stark reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked 91, 300577; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1619 ZBTB16 Zornitza Stark Mode of inheritance for gene: ZBTB16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1617 ZBTB16 Zornitza Stark reviewed gene: ZBTB16: Rating: AMBER; Mode of pathogenicity: None; Publications: 18611983; Phenotypes: Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1617 ZBTB11 Zornitza Stark Phenotypes for gene: ZBTB11 were changed from to Intellectual developmental disorder, autosomal recessive 69, OMIM #618383
Mendeliome v0.1615 ZBTB11 Zornitza Stark Mode of inheritance for gene: ZBTB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1613 ZBTB11 Zornitza Stark reviewed gene: ZBTB11: Rating: AMBER; Mode of pathogenicity: None; Publications: 29893856; Phenotypes: Intellectual developmental disorder, autosomal recessive 69, OMIM #618383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1611 WNT3 Zornitza Stark Mode of inheritance for gene: WNT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1609 WNT3 Zornitza Stark reviewed gene: WNT3: Rating: RED; Mode of pathogenicity: None; Publications: 14872406; Phenotypes: Tetra-amelia syndrome 1, MIM# 273395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1607 RS1 Zornitza Stark Mode of inheritance for gene: RS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1604 SMC1A Zornitza Stark Mode of inheritance for gene: SMC1A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1601 AIRE Zornitza Stark Mode of inheritance for gene: AIRE was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1600 AIRE Zornitza Stark Mode of inheritance for gene: AIRE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1599 LOXHD1 Zornitza Stark Phenotypes for gene: LOXHD1 were changed from to Deafness, autosomal recessive 77, MIM# 613079
Mendeliome v0.1597 LOXHD1 Zornitza Stark Mode of inheritance for gene: LOXHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1596 LOXHD1 Zornitza Stark reviewed gene: LOXHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732867, 25792669; Phenotypes: Deafness, autosomal recessive 77, MIM# 613079; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1596 WFS1 Zornitza Stark Phenotypes for gene: WFS1 were changed from to ?Cataract 41; Deafness, autosomal dominant 6/14/38; Wolfram syndrome, autosomal recessive 1; Wolfram-like syndrome, autosomal dominant; {Diabetes mellitus, noninsulin-dependent, association with}
Mendeliome v0.1594 WFS1 Zornitza Stark Mode of inheritance for gene: WFS1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1590 RS1 Kristin Rigbye reviewed gene: RS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15932525, 23453514, 23847049; Phenotypes: Retinoschisis, 312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1590 SMC1A Melanie Marty reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273969, 22106055, 19701948, 26752331, 28166369; Phenotypes: Cornelia de Lange syndrome 2 300590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1590 AIRE Teresa Zhao reviewed gene: AIRE: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1590 WFS1 Teresa Zhao reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25211237; Phenotypes: ?Cataract 41, Deafness, autosomal dominant 6/14/38, Wolfram syndrome 1, Wolfram-like syndrome, autosomal dominant, {Diabetes mellitus, noninsulin-dependent, association with}; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1589 VARS Zornitza Stark Mode of inheritance for gene: VARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1588 VARS Zornitza Stark reviewed gene: VARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30755616, 30755602, 26539891, 29691655, 30275004; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, OMIM #617802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1584 KRT6A Zornitza Stark Mode of inheritance for gene: KRT6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1583 TUBA8 Zornitza Stark Phenotypes for gene: TUBA8 were changed from to Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180
Mendeliome v0.1581 TUBA8 Zornitza Stark Mode of inheritance for gene: TUBA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1579 TUBA8 Zornitza Stark reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1577 RPL26 Zornitza Stark Mode of inheritance for gene: RPL26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1575 RPL26 Zornitza Stark reviewed gene: RPL26: Rating: RED; Mode of pathogenicity: None; Publications: 22431104; Phenotypes: Diamond-Blackfan anemia 11, MIM# 614900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1575 KRT6A Crystle Lee reviewed gene: KRT6A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 21326300; Phenotypes: Pachyonychia congenita 3 (MIM#615726); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1572 ABCC6 Zornitza Stark Mode of inheritance for gene: ABCC6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1571 ABCC6 Zornitza Stark Mode of inheritance for gene: ABCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1570 ABCC6 Ain Roesley reviewed gene: ABCC6: Rating: ; Mode of pathogenicity: None; Publications: PMID: 11536079; Phenotypes: Pseudoxanthoma elasticum (MIM# 264800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1568 TRIM8 Zornitza Stark Mode of inheritance for gene: TRIM8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1567 TRIM8 Zornitza Stark reviewed gene: TRIM8: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244534, 27346735, 23934111; Phenotypes: Intellectual disability, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1565 TPH2 Zornitza Stark Mode of inheritance for gene: TPH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1563 TPH2 Zornitza Stark reviewed gene: TPH2: Rating: RED; Mode of pathogenicity: None; Publications: 18347598; Phenotypes: {Attention deficit-hyperactivity disorder, susceptibility to, 7} 613003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1562 SPOP Zornitza Stark gene: SPOP was added
gene: SPOP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPOP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPOP were set to 32109420
Phenotypes for gene: SPOP were set to Intellectual disability; dysmorphism; microcephaly; macrocephaly
Mode of pathogenicity for gene: SPOP was set to Other
Review for gene: SPOP was set to GREEN
Added comment: Seven individuals reported with de novo missense variants in this gene. Gain-of-function variants associated with microcephaly whereas dominant-negative variants associated with macrocephaly.
Sources: Literature
Mendeliome v0.1561 TNIK Zornitza Stark Phenotypes for gene: TNIK were changed from to Mental retardation, autosomal recessive 54, MIM# 617028
Mendeliome v0.1559 TNIK Zornitza Stark Mode of inheritance for gene: TNIK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1557 TNIK Zornitza Stark reviewed gene: TNIK: Rating: AMBER; Mode of pathogenicity: None; Publications: 27106596, 23035106; Phenotypes: Mental retardation, autosomal recessive 54, MIM# 617028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1555 TMLHE Zornitza Stark Mode of inheritance for gene: TMLHE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1554 TMLHE Zornitza Stark reviewed gene: TMLHE: Rating: GREEN; Mode of pathogenicity: None; Publications: 21865298; Phenotypes: {Autism, susceptibility to, X-linked 6}, MIM#300872; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1553 TMEM94 Zornitza Stark gene: TMEM94 was added
gene: TMEM94 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to 30526868
Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies, MIM#618316
Review for gene: TMEM94 was set to GREEN
Added comment: 10 individuals from 6 unrelated families.
Sources: Expert list
Mendeliome v0.1552 TMEM260 Zornitza Stark Phenotypes for gene: TMEM260 were changed from to Structural heart defects and renal anomalies syndrome, MIM# 617478
Mendeliome v0.1550 TMEM260 Zornitza Stark Mode of inheritance for gene: TMEM260 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1548 TMEM260 Zornitza Stark reviewed gene: TMEM260: Rating: AMBER; Mode of pathogenicity: None; Publications: 28318500; Phenotypes: Structural heart defects and renal anomalies syndrome, MIM# 617478; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1546 TKT Zornitza Stark Mode of inheritance for gene: TKT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1544 TKT Zornitza Stark reviewed gene: TKT: Rating: AMBER; Mode of pathogenicity: None; Publications: 27259054; Phenotypes: Short stature, developmental delay, and congenital heart defects, OMIM #617044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1542 TELO2 Zornitza Stark Mode of inheritance for gene: TELO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1541 TELO2 Zornitza Stark reviewed gene: TELO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27132593, 28944240; Phenotypes: You-Hoover-Fong syndrome, MIM#616954, Syndromic intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1541 TECR Zornitza Stark Phenotypes for gene: TECR were changed from to Mental retardation, autosomal recessive, MIM#614020
Mendeliome v0.1539 TECR Zornitza Stark Mode of inheritance for gene: TECR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1537 TECR Zornitza Stark reviewed gene: TECR: Rating: RED; Mode of pathogenicity: None; Publications: 21212097; Phenotypes: Mental retardation, autosomal recessive, MIM#614020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1537 TBC1D7 Zornitza Stark Phenotypes for gene: TBC1D7 were changed from to Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000
Mendeliome v0.1535 TBC1D7 Zornitza Stark Mode of inheritance for gene: TBC1D7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1533 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1533 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from to Mental retardation, autosomal recessive 40, MIM# 615599
Mendeliome v0.1531 TAF2 Zornitza Stark Mode of inheritance for gene: TAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1529 TAF2 Zornitza Stark reviewed gene: TAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40, MIM# 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1529 TAF13 Zornitza Stark Phenotypes for gene: TAF13 were changed from to Mental retardation, autosomal recessive 60, MIM# 617432
Mendeliome v0.1527 TAF13 Zornitza Stark Mode of inheritance for gene: TAF13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1525 TAF13 Zornitza Stark reviewed gene: TAF13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257693; Phenotypes: Mental retardation, autosomal recessive 60, MIM# 617432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1525 SYT14 Zornitza Stark Phenotypes for gene: SYT14 were changed from to Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229
Mendeliome v0.1523 SYT14 Zornitza Stark Mode of inheritance for gene: SYT14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1521 SYT14 Zornitza Stark reviewed gene: SYT14: Rating: RED; Mode of pathogenicity: None; Publications: 21835308; Phenotypes: Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1519 SRPX2 Zornitza Stark Mode of inheritance for gene: SRPX2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1517 SRPX2 Zornitza Stark reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: 16497722, 23933820, 23871722; Phenotypes: Rolandic epilepsy, mental retardation, and speech dyspraxia, MIM# 300643; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1515 SPRTN Zornitza Stark Mode of inheritance for gene: SPRTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1514 SPRTN Zornitza Stark reviewed gene: SPRTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25261934; Phenotypes: Ruijs-Aalfs syndrome, MIM# 616200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1512 MC4R Zornitza Stark Mode of inheritance for gene: MC4R was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1509 KMT2A Zornitza Stark Mode of inheritance for gene: KMT2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1506 RBM20 Zornitza Stark Mode of inheritance for gene: RBM20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1505 RBM20 Zornitza Stark reviewed gene: RBM20: Rating: GREEN; Mode of pathogenicity: None; Publications: 30871351; Phenotypes: Cardiomyopathy, dilated, 1DD 613172 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1503 SLC52A1 Zornitza Stark Mode of inheritance for gene: SLC52A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1501 PTCH2 Zornitza Stark reviewed gene: PTCH2: Rating: RED; Mode of pathogenicity: None; Publications: 30820324, 23479190, 18285427; Phenotypes: Basal cell nevus syndrome, MIM#109400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1498 PTCH2 Zornitza Stark Mode of inheritance for gene: PTCH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1496 ZNF592 Chern Lim changed review comment from: No patients reported with ZNF592 variant that is clearly disease causing.

A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly supportive of pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727).; to: No patients reported with ZNF592 variant that is clearly disease causing.

A 2010 paper published a biallelic missense variant segregating in one family with non-progressive, autosomal recessive, congenital cerebellar ataxia; however functional data not strongly conclusive for pathogenicity (PMID: 20531441). Same authors later identified a homozygous WDR73 variant in that family which explains the phenotype (PMID: 26123727).
Mendeliome v0.1494 COL2A1 Zornitza Stark Mode of inheritance for gene: COL2A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1493 DNMT1 Zornitza Stark Phenotypes for gene: DNMT1 were changed from to Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121; Neuropathy, hereditary sensory, type IE, 614116
Mendeliome v0.1491 DNMT1 Zornitza Stark Mode of inheritance for gene: DNMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1490 CEP135 Zornitza Stark Phenotypes for gene: CEP135 were changed from to Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673
Mendeliome v0.1488 CEP135 Zornitza Stark Mode of inheritance for gene: CEP135 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1486 CYP21A2 Zornitza Stark Mode of inheritance for gene: CYP21A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1483 CDK13 Zornitza Stark Mode of inheritance for gene: CDK13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1482 CDK13 Zornitza Stark reviewed gene: CDK13: Rating: GREEN; Mode of pathogenicity: None; Publications: 29021403, 29393965, 30904094; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM#617360; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1480 F13B Zornitza Stark Mode of inheritance for gene: F13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1477 FMO3 Zornitza Stark Mode of inheritance for gene: FMO3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1476 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from to Boucher-Neuhauser syndrome, 215470; ?Laurence-Moon syndrome, 245800; Oliver-McFarlane syndrome, 275400; Spastic paraplegia 39, autosomal recessive, 612020
Mendeliome v0.1474 PNPLA6 Zornitza Stark Mode of inheritance for gene: PNPLA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 MC4R Michelle Torres reviewed gene: MC4R: Rating: GREEN; Mode of pathogenicity: None; Publications: 29970488; Phenotypes: {Obesity, resistence to (BMIQ20)} 618306, Obesity (BMIQ20) 618406 AD, AR; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1473 KMT2A Michelle Torres reviewed gene: KMT2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 16990798; Phenotypes: Leukemia, myeloid/lymphoid or mixed-lineage 159555 AD, Wiedemann-Steiner syndrome 605130 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.1473 SLC52A1 Kristin Rigbye reviewed gene: SLC52A1: Rating: RED; Mode of pathogenicity: None; Publications: 29122468, 17689999; Phenotypes: Riboflavin deficiency, 615026; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1473 PTCH2 Kristin Rigbye reviewed gene: PTCH2: Rating: RED; Mode of pathogenicity: None; Publications: 30820324; Phenotypes: Basal cell carcinoma, somatic 605462, Basal cell nevus syndrome, 109400, Medulloblastoma, somatic; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1473 COL2A1 Elena Savva reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15895462, 17721977, 27234559, 20179744; Phenotypes: Achondrogenesis, type II or hypochondrogenesis 200610, Avascular necrosis of the femoral head 608805, Czech dysplasia 609162, Epiphyseal dysplasia, multiple, with myopia and deafness 132450, Kniest dysplasia 156550, Legg-Calve-Perthes disease 150600, Osteoarthritis with mild chondrodysplasia 604864, Platyspondylic skeletal dysplasia, Torrance type 151210, SED congenita 183900, SMED Strudwick type 184250, Spondyloepiphyseal dysplasia, Stanescu type 616583, Spondyloperipheral dysplasia 271700, Stickler sydrome, type I, nonsyndromic ocular 609508, Stickler syndrome, type I 108300, Vitreoretinopathy with phalangeal epiphyseal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.1473 DNMT1 Elena Savva reviewed gene: DNMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22328086, 21532572; Phenotypes: Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, 604121, Neuropathy, hereditary sensory, type IE, 614116; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1473 CEP135 Elena Savva reviewed gene: CEP135: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 CEP135 Elena Savva reviewed gene: CEP135: Rating: ; Mode of pathogenicity: None; Publications: PMID: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: None
Mendeliome v0.1473 CYP21A2 Elena Savva reviewed gene: CYP21A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency, 201910, Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency, 201910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 F13B Elena Savva reviewed gene: F13B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20331752, 26247044; Phenotypes: Factor XIIIB deficiency, 613235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 FMO3 Elena Savva reviewed gene: FMO3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28649550, 31240165; Phenotypes: Trimethylaminuria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 PNPLA6 Elena Savva reviewed gene: PNPLA6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25480986, 24355708; Phenotypes: Boucher-Neuhauser syndrome, 215470, ?Laurence-Moon syndrome, 245800, Oliver-McFarlane syndrome, 275400, Spastic paraplegia 39, autosomal recessive, 612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1473 CEP85L Zornitza Stark gene: CEP85L was added
gene: CEP85L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097630
Phenotypes for gene: CEP85L were set to Lissencephaly, posterior predominant
Review for gene: CEP85L was set to GREEN
Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects.
Sources: Literature
Mendeliome v0.1469 SOBP Zornitza Stark Mode of inheritance for gene: SOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1467 SOBP Zornitza Stark reviewed gene: SOBP: Rating: RED; Mode of pathogenicity: None; Publications: 21035105; Phenotypes: Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1465 SNIP1 Zornitza Stark Mode of inheritance for gene: SNIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1463 SNIP1 Zornitza Stark reviewed gene: SNIP1: Rating: RED; Mode of pathogenicity: None; Publications: 22279524; Phenotypes: Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1463 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from to Heart and brain malformation syndrome, MIM# 616920
Mendeliome v0.1461 SMG9 Zornitza Stark Mode of inheritance for gene: SMG9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1460 SMG9 Zornitza Stark reviewed gene: SMG9: Rating: GREEN; Mode of pathogenicity: None; Publications: 27018474, 31390136; Phenotypes: Heart and brain malformation syndrome, MIM# 616920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1459 TMPRSS3 Zornitza Stark Phenotypes for gene: TMPRSS3 were changed from to Deafness, autosomal recessive 8/10, MIM#601072
Mendeliome v0.1458 TMPRSS3 Zornitza Stark Mode of inheritance for gene: TMPRSS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1457 TMPRSS3 Zornitza Stark reviewed gene: TMPRSS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21786053, 17551081; Phenotypes: Deafness, autosomal recessive 8/10, MIM#601072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1455 POU3F4 Zornitza Stark Mode of inheritance for gene: POU3F4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1452 SLIT2 Zornitza Stark Mode of inheritance for gene: SLIT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1450 SLIT2 Zornitza Stark reviewed gene: SLIT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26026792, 15130495; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1448 CEL Zornitza Stark Mode of inheritance for gene: CEL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1446 CEL Zornitza Stark reviewed gene: CEL: Rating: AMBER; Mode of pathogenicity: None; Publications: 24062244, 21784842, 19760265, 18544793, 17989309, 16369531, 29233499, 27650499; Phenotypes: Maturity-onset diabetes of the young, type VIII; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1446 WDR81 Zornitza Stark Phenotypes for gene: WDR81 were changed from to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185; Hydrocephalus, congenital, 3, with brain anomalies, 617967
Mendeliome v0.1444 WDR81 Zornitza Stark Mode of inheritance for gene: WDR81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1443 ARSG Zornitza Stark gene: ARSG was added
gene: ARSG was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSG were set to 29300381; 20679209; 25452429; 26975023
Phenotypes for gene: ARSG were set to Usher syndrome, type IV, MIM# 618144
Review for gene: ARSG was set to RED
Added comment: Atypical late-onset RP/HL phenotype described in 5 individuals from three Yemenite Jewish families. Same homozygous missense variant identified in all, founder effect. Animal models associated with neuronal ceroid lipofuscinosis.
Sources: Expert list
Mendeliome v0.1442 OTOF Zornitza Stark Phenotypes for gene: OTOF were changed from to Auditory neuropathy, autosomal recessive, 1 (MIM # 601071); Deafness, autosomal recessive 9 (MIM # 601071)
Mendeliome v0.1440 OTOF Zornitza Stark Mode of inheritance for gene: OTOF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1439 OTOF Zornitza Stark reviewed gene: OTOF: Rating: GREEN; Mode of pathogenicity: None; Publications: 16371502, 22906306; Phenotypes: Auditory neuropathy, autosomal recessive, 1 (MIM # 601071), Deafness, autosomal recessive 9 (MIM # 601071); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1438 MYL1 Bryony Thompson gene: MYL1 was added
gene: MYL1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL1 were set to 30215711
Phenotypes for gene: MYL1 were set to Myopathy, congenital, with fast-twitch (type II) fiber atrophy MIM#618414
Review for gene: MYL1 was set to AMBER
Added comment: Two probands with congenital myopathy and a zebrafish model. Probably need one more family to push it over the line.
Sources: NHS GMS
Mendeliome v0.1436 FXR1 Bryony Thompson gene: FXR1 was added
gene: FXR1 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: FXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXR1 were set to 30770808
Phenotypes for gene: FXR1 were set to Congenital multi-minicore myopathy
Review for gene: FXR1 was set to GREEN
Added comment: Two unrelated families and a mouse model with non-lethal myopathy phenotype.
Sources: NHS GMS
Mendeliome v0.1435 POU3F4 Elena Savva reviewed gene: POU3F4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31786483, 30176854; Phenotypes: Deafness, X-linked 2; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1435 WDR81 Kristin Rigbye reviewed gene: WDR81: Rating: GREEN; Mode of pathogenicity: None; Publications: 21885617, 28556411; Phenotypes: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185, Hydrocephalus, congenital, 3, with brain anomalies, 617967; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1433 TBCE Zornitza Stark Mode of inheritance for gene: TBCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1432 HTRA1 Zornitza Stark Phenotypes for gene: HTRA1 were changed from to {Macular degeneration, age-related, 7}, 6101493; {Macular degeneration, age-related, neovascular type}, 610149; CARASIL syndrome, 600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779
Mendeliome v0.1429 HTRA1 Zornitza Stark Mode of inheritance for gene: HTRA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1426 PLPBP Zornitza Stark Mode of inheritance for gene: PLPBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1422 PTPN11 Zornitza Stark Mode of inheritance for gene: PTPN11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1421 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from to Arthrogryposis multiplex congenita, myogenic type, MIM# 618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant, MIM# 612998; Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743
Mendeliome v0.1419 SYNE1 Zornitza Stark Mode of inheritance for gene: SYNE1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1418 SYNE1 Zornitza Stark edited their review of gene: SYNE1: Added comment: Well established gene-disease association with Emery-Dreifuss muscular dystrophy (AD), and with recessive ataxia.
Distal arthrogryposis: three families reported with bi-allelic distal truncating variants in the KASH domain. This appears to be a specific genotype-phenotype correlation.; Changed rating: GREEN; Changed publications: 23352163, 27782104; Changed phenotypes: Arthrogryposis multiplex congenita, myogenic type, MIM# 618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant, MIM# 612998, Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1418 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934)
Mendeliome v0.1416 PNPT1 Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1415 TBCE Elena Savva reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27666369; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy, Hypoparathyroidism-retardation-dysmorphism syndrome, Kenny-Caffey syndrome, type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1415 HTRA1 Elena Savva reviewed gene: HTRA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29895533, 19387015; Phenotypes: {Macular degeneration, age-related, 7}, 6101493, {Macular degeneration, age-related, neovascular type}, 610149, CARASIL syndrome, 600142, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, 616779; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1415 PLPBP Elena Savva reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29689137, 27912044; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, 617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1415 PTPN11 Crystle Lee reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 24935154, 11704759, 21533187; Phenotypes: LEOPARD syndrome 1 (MIM#151100), Noonan syndrome 1 (MIM#163950), Metachondromatosis (MIM#156250); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1415 SYNE1 Crystle Lee reviewed gene: SYNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30573412; Phenotypes: Spinocerebellar ataxia, autosomal recessive 8 (MIM#610743); Mode of inheritance: None
Mendeliome v0.1415 PNPT1 Crystle Lee reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31752325, PMID: 30244537, PMID: 28594066, PMID: 28645153; Phenotypes: Combined oxidative phosphorylation deficiency 13 (MIM#614932), Deafness, autosomal recessive 70 (MIM#614934); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1410 AANAT Zornitza Stark Mode of inheritance for gene: AANAT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1408 AANAT Zornitza Stark reviewed gene: AANAT: Rating: RED; Mode of pathogenicity: None; Publications: 12736803; Phenotypes: Delayed sleep phase, susceptibility to; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1407 DUX4 Zornitza Stark Mode of inheritance for gene: DUX4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1405 DUX4 Zornitza Stark reviewed gene: DUX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fascioscapulohumeral muscular dystrophy, MIM#158900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1403 SLC6A4 Zornitza Stark Mode of inheritance for gene: SLC6A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1401 SLC6A4 Zornitza Stark reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: 31629822; Phenotypes: {Obsessive-compulsive disorder}, MIM# 164230, depression, alcohol dependence; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1396 HGSNAT Zornitza Stark Mode of inheritance for gene: HGSNAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1393 PNKP Zornitza Stark Mode of inheritance for gene: PNKP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1390 DNAH5 Zornitza Stark Mode of inheritance for gene: DNAH5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1389 CDH23 Zornitza Stark Phenotypes for gene: CDH23 were changed from to Usher syndrome, type 1D (MIM# 601067); Deafness, autosomal recessive 12 (MIM # 601386) Usher syndrome, type 1D/F digenic (MIM #601067)
Mendeliome v0.1387 CDH23 Zornitza Stark Mode of inheritance for gene: CDH23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 HGSNAT Ain Roesley reviewed gene: HGSNAT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19479962, 31228227, 20825431, 20583299; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C) (MIM #252930), Retinitis pigmentosa 73 (MIM # 616544); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 PNKP Kristin Rigbye reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31436889, 31707899; Phenotypes: Ataxia-oculomotor apraxia 4, Microcephaly, seizures, and developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1386 DNAH5 Ain Roesley reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16627867; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus (MIM #608644); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1386 CDH23 Ain Roesley reviewed gene: CDH23: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11138009, 25468891, 21940737; Phenotypes: Usher syndrome, type 1D (MIM# 601067), Deafness, autosomal recessive 12 (MIM # 601386) Usher syndrome, type 1D/F digenic (MIM #601067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1384 SHROOM4 Zornitza Stark Mode of inheritance for gene: SHROOM4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1382 SHROOM4 Zornitza Stark reviewed gene: SHROOM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 16249884, 26740508; Phenotypes: Stocco dos Santos X-linked mental retardation syndrome, 300434, Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1380 F2 Zornitza Stark Mode of inheritance for gene: F2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1379 F2 Zornitza Stark reviewed gene: F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30297698; Phenotypes: {Pregnancy loss, recurrent, susceptibility to, 2} 614390 AD, {Stroke, ischemic, susceptibility to} 601367 Mu, Dysprothrombinemia 613679 AR, Hypoprothrombinemia 613679 AR, Thrombophilia due to thrombin defect 188050 AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1378 CHD2 Zornitza Stark Mode of inheritance for gene: CHD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1375 INTS1 Zornitza Stark Mode of inheritance for gene: INTS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1374 INTS1 Zornitza Stark reviewed gene: INTS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28542170, 30622326, 31428919; Phenotypes: Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, MIM# 618571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1373 CHD2 Teresa Zhao reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, childhood-onset (MIM # 615369); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.1373 SOX3 Zornitza Stark Phenotypes for gene: SOX3 were changed from Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123; Panhypopituitarism, X-linked, MIM#312000 to Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123; Panhypopituitarism, X-linked, MIM#312000; XX male sex reversal
Mendeliome v0.1372 SOX3 Zornitza Stark edited their review of gene: SOX3: Changed phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000, XX male sex reversal
Mendeliome v0.1370 SOX3 Zornitza Stark Mode of inheritance for gene: SOX3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1368 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29175558, 30125608, 12428212, 15800844; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1368 AKT1 Zornitza Stark Mode of inheritance for gene: AKT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1362 PEX6 Zornitza Stark Mode of inheritance for gene: PEX6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1360 PUF60 Zornitza Stark Mode of inheritance for gene: PUF60 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1358 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1357 AKT1 Elena Savva reviewed gene: AKT1: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 23246288; Phenotypes: Cowden syndrome 6, Proteus syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1357 PEX6 Elena Savva reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29220678; Phenotypes: Peroxisome biogenesis disorder 4B, Heimler syndrome 2, Peroxisome biogenesis disorder 4A (Zellweger); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1357 PUF60 Elena Savva reviewed gene: PUF60: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Verheij syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1357 KMT2E Elena Savva reviewed gene: KMT2E: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31079897; Phenotypes: O'Donnell-Luria-Rodan syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1357 ATRX Elena Savva reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha-thalassemia myelodysplasia syndrome, somatic, Alpha-thalassemia/mental retardation syndrome, Mental retardation-hypotonic facies syndrome, X-linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1356 PTRHD1 Zornitza Stark gene: PTRHD1 was added
gene: PTRHD1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PTRHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRHD1 were set to 30398675; 27134041; 27753167; 29143421
Phenotypes for gene: PTRHD1 were set to Parkinsonism; Intellectual disability
Review for gene: PTRHD1 was set to GREEN
Added comment: Three unrelated families reported: two with homozygous missense variants; and one with truncating variant. Affected individuals have juvenile-onset parkinsonism and ID.
Sources: Expert list
Mendeliome v0.1353 GFER Zornitza Stark Mode of inheritance for gene: GFER was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1349 KRT14 Zornitza Stark Mode of inheritance for gene: KRT14 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1348 KRT14 Zornitza Stark reviewed gene: KRT14: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960809, 18049449; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1348 GFER Ain Roesley reviewed gene: GFER: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28155230; Phenotypes: Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay (MIM #613076); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1346 PITRM1 Zornitza Stark gene: PITRM1 was added
gene: PITRM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PITRM1 were set to 26697887; 29764912; 29383861
Phenotypes for gene: PITRM1 were set to Ataxia; Intellectual disability
Review for gene: PITRM1 was set to GREEN
gene: PITRM1 was marked as current diagnostic
Added comment: Three unrelated families reported with bi-allelic variants in this gene.
Sources: Expert list
Mendeliome v0.1344 CSGALNACT1 Tiong Tan gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Mendeliome. Sources: Expert Review,Literature
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CSGALNACT1 were set to Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age
Review for gene: CSGALNACT1 was set to GREEN
Added comment: Two unrelated families and functional studies
Sources: Expert Review, Literature
Mendeliome v0.1341 UNC13A Zornitza Stark Mode of inheritance for gene: UNC13A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1339 UNC13A Zornitza Stark reviewed gene: UNC13A: Rating: RED; Mode of pathogenicity: None; Publications: 27648472, 28192369; Phenotypes: Congenital myasthenia, dyskinesia, autism, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1338 TOR1AIP1 Bryony Thompson gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 31299614; 30723199; 27342937
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures MIM#617072
Review for gene: TOR1AIP1 was set to GREEN
Added comment: At least 5 families/cases reported with muscular dystrophy and sometimes cardiomyopathy.
Sources: Expert list
Mendeliome v0.1337 BCKDHB Melanie Marty reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type Ib 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1335 EML1 Zornitza Stark Mode of inheritance for gene: EML1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1333 ELMO2 Zornitza Stark gene: ELMO2 was added
gene: ELMO2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ELMO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELMO2 were set to 27476657
Phenotypes for gene: ELMO2 were set to Vascular malformation, primary intraosseous, MIM#606893
Review for gene: ELMO2 was set to GREEN
Added comment: Five unrelated families reported.
Sources: Expert list
Mendeliome v0.1327 EML1 Ain Roesley reviewed gene: EML1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31710781; Phenotypes: Band heterotopia (MIM# 600348); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1325 MAP3K20 Bryony Thompson gene: MAP3K20 was added
gene: MAP3K20 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MAP3K20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAP3K20 were set to 27816943; 26755636
Phenotypes for gene: MAP3K20 were set to Centronuclear myopathy 6 with fiber-type disproportion MIM#617760; Split-foot malformation with mesoaxial polydactyly MIM#616890
Review for gene: MAP3K20 was set to GREEN
Added comment: 3 unrelated consanguineous families homozygous for 3 different variants with centronuclear myopathy, and at least 2 families reported with split-foot malformation. Null mouse model is embryonic lethal due to severe cardiac edema and growth retardation. Gene alias of ZAK used in the published studies.
Sources: Expert list
Mendeliome v0.1322 PCDH10 Zornitza Stark Mode of inheritance for gene: PCDH10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1320 PCDH10 Zornitza Stark reviewed gene: PCDH10: Rating: RED; Mode of pathogenicity: None; Publications: 27567313, 18621663; Phenotypes: Autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1318 LNPK Zornitza Stark Mode of inheritance for gene: LNPK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1316 LNPK Zornitza Stark reviewed gene: LNPK: Rating: AMBER; Mode of pathogenicity: None; Publications: 30032983; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1314 KIF4A Zornitza Stark Mode of inheritance for gene: KIF4A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1312 KIF4A Zornitza Stark reviewed gene: KIF4A: Rating: RED; Mode of pathogenicity: None; Publications: 24812067; Phenotypes: Mental retardation, X-linked 100, MIM# 300923; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1309 KCNK4 Zornitza Stark Mode of inheritance for gene: KCNK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1308 KCNK4 Zornitza Stark reviewed gene: KCNK4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30290154; Phenotypes: Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome 618381; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1306 INTS8 Zornitza Stark Mode of inheritance for gene: INTS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1304 INTS8 Zornitza Stark reviewed gene: INTS8: Rating: RED; Mode of pathogenicity: None; Publications: 28542170; Phenotypes: Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, MIM# 618572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1302 SCO2 Zornitza Stark Mode of inheritance for gene: SCO2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1299 IDUA Zornitza Stark Mode of inheritance for gene: IDUA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1296 AHI1 Zornitza Stark Mode of inheritance for gene: AHI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1293 TGM5 Zornitza Stark Mode of inheritance for gene: TGM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1292 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from to ?Epidermolysis bullosa simplex with nail dystrophy, MIM# 616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
Mendeliome v0.1290 PLEC Zornitza Stark Mode of inheritance for gene: PLEC was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1289 SCO2 Elena Savva reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31844624, 29351582, 26427993; Phenotypes: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, Myopia 6, Charcot-Marie-Tooth type 4, Cerebellar ataxia and progressive peripheral axonal neuropthy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1289 IDUA Crystle Lee reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28752568, 12865757; Phenotypes: Mucopolysaccharidosis Ih (MIM#607014), Mucopolysaccharidosis Ih/s (MIM#607015), Mucopolysaccharidosis Is (MIM#6070); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1289 AHI1 Elena Savva reviewed gene: AHI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25616960; Phenotypes: Joubert syndrome 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1289 TGM5 Elena Savva reviewed gene: TGM5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16380904; Phenotypes: Peeling skin syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1289 PLEC Elena Savva reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22144912; Phenotypes: ?Epidermolysis bullosa simplex with nail dystrophy, Epidermolysis bullosa simplex with muscular dystrophy, Epidermolysis bullosa simplex with pyloric atresia, Epidermolysis bullosa simplex, Ogna type, Muscular dystrophy, limb-girdle; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1287 HSPG2 Zornitza Stark Mode of inheritance for gene: HSPG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1285 WNT10A Elena Savva reviewed gene: WNT10A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19559398, 30426266; Phenotypes: Odontoonychodermal dysplasia, Schopf-Schulz-Passarge syndrome, Tooth agenesis, selective, 4; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1284 BEST1 Zornitza Stark Phenotypes for gene: BEST1 were changed from to Bestrophinopathy, autosomal recessive, MIM# 611809; Macular dystrophy, vitelliform, 2 MIM# 153700; Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma, MIM# 193220; Retinitis pigmentosa-50, MIM# 613194; Retinitis pigmentosa, concentric, MIM# 61319; Vitreoretinochoroidopathy,MIM# 193220
Mendeliome v0.1283 BEST1 Zornitza Stark Mode of inheritance for gene: BEST1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1280 IGBP1 Zornitza Stark Mode of inheritance for gene: IGBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1278 IGBP1 Zornitza Stark reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: 14556245; Phenotypes: Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1278 HSPG2 Elena Savva reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16927315; Phenotypes: Dyssegmental dysplasia, Silverman-Handmaker type, Schwartz-Jampel syndrome, type 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1275 IQSEC2 Zornitza Stark Mode of inheritance for gene: IQSEC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1274 IQSEC2 Elena Savva reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31415821, 20473311, 30842726; Phenotypes: Mental retardation, X-linked 1/78; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.1273 GRIA1 Zornitza Stark gene: GRIA1 was added
gene: GRIA1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GRIA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Phenotypes for gene: GRIA1 were set to Intellectual disability; autism
Review for gene: GRIA1 was set to GREEN
Added comment: Multiple affected individuals reported but in large ID cohorts reporting multiple candidate genes. Recurrent (p.A636T) variant.
Sources: Expert list
Mendeliome v0.1268 HDAC4 Zornitza Stark Mode of inheritance for gene: HDAC4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1264 UBR4 Zornitza Stark Mode of inheritance for gene: UBR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1262 UBR4 Zornitza Stark reviewed gene: UBR4: Rating: AMBER; Mode of pathogenicity: None; Publications: 29062094, 23982692, 28600779; Phenotypes: Episodic ataxia, progressive neurological deterioration; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1262 HDAC4 Elena Savva reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 24715439, 20691407, 31209962; Phenotypes: Brachydactyly mental retardation syndrome, Brachydactyly without intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1260 GMNN Zornitza Stark Mode of inheritance for gene: GMNN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1259 GMNN Zornitza Stark reviewed gene: GMNN: Rating: GREEN; Mode of pathogenicity: None; Publications: 26637980; Phenotypes: Meier-Gorlin syndrome 6, MIM# 616835; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1258 TRAPPC4 Zornitza Stark gene: TRAPPC4 was added
gene: TRAPPC4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC4 were set to 31794024
Phenotypes for gene: TRAPPC4 were set to intellectual disability; epilepsy; spasticity; microcephaly
Review for gene: TRAPPC4 was set to GREEN
Added comment: Seven individuals from three unrelated families reported; recurrent splice site variant (hg19:chr11:g.118890966A>G; TRAPPC4: NM_016146.5; c.454+3A>G), not a founder variant.
Sources: Expert Review
Mendeliome v0.1256 SNX27 Zornitza Stark gene: SNX27 was added
gene: SNX27 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SNX27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX27 were set to 25894286; 31721175; 21300787; 23524343
Phenotypes for gene: SNX27 were set to intellectual disability; seizures
Review for gene: SNX27 was set to GREEN
Added comment: Three unrelated families and animal model.
Sources: Expert Review
Mendeliome v0.1254 NSF Zornitza Stark gene: NSF was added
gene: NSF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSF were set to 31675180
Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Review for gene: NSF was set to AMBER
Added comment: Two individuals reported with de novo missense variants in this gene.
Sources: Literature
Mendeliome v0.1252 KAT8 Zornitza Stark gene: KAT8 was added
gene: KAT8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KAT8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT8 were set to 31794431
Phenotypes for gene: KAT8 were set to Intellectual disability; seizures; autism; dysmorphic features
Review for gene: KAT8 was set to GREEN
Added comment: Eight unrelated individuals reported with de novo variants in this gene and a mouse model. All variants missense, in the chromobarrel domain or the acetyltransferase domain; three individuals had the same variant p.Tyr90Cys . One more individual reported with bi-allelic variants: one missense and one frameshift; carrier parents were normal suggesting that may be haploinsuffiency is not the mechanism.
Sources: Literature
Mendeliome v0.1249 GABBR2 Zornitza Stark Mode of inheritance for gene: GABBR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1248 GABBR2 Zornitza Stark reviewed gene: GABBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083, 28061363, 28135719, 28856709, 29369404, 29377213; Phenotypes: Neurodevelopmental disorder with poor language and loss of hand skills, 617903; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1245 HNRNPU Zornitza Stark Mode of inheritance for gene: HNRNPU was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1243 SERPINI1 Zornitza Stark Mode of inheritance for gene: SERPINI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1242 SERPINI1 Zornitza Stark reviewed gene: SERPINI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28631894, 25401298, 12103288; Phenotypes: Encephalopathy, familial, with neuroserpin inclusion bodies MIM#604218; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1240 TTC7A Zornitza Stark Mode of inheritance for gene: TTC7A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1239 HNRNPU Crystle Lee reviewed gene: HNRNPU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28944577, 28393272; Phenotypes: Epileptic encephalopathy, early infantile, 54 (MIM#617391); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1239 TTC7A Melanie Marty reviewed gene: TTC7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30553809, 28936210; Phenotypes: Gastrointestinal defects and immunodeficiency syndrome, 243150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1238 OPA1 Zornitza Stark Mode of inheritance for gene: OPA1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.1237 SASS6 Zornitza Stark Phenotypes for gene: SASS6 were changed from to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Mendeliome v0.1235 SASS6 Zornitza Stark Mode of inheritance for gene: SASS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1233 SASS6 Zornitza Stark reviewed gene: SASS6: Rating: AMBER; Mode of pathogenicity: None; Publications: 24951542, 30639237; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM# 616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1230 ACTB Sebastian Lunke Mode of inheritance for gene: ACTB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1222 CNTN1 Zornitza Stark Mode of inheritance for gene: CNTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1220 OPA1 Ee Ming Wong reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30165240; Phenotypes: 1. ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) 6168963, 2. {Glaucoma, normal tension, susceptibility to} 6066573, 3. Behr syndrome 210000 AR, 4. Optic atrophy 1 165500 AD, 5. Optic atrophy plus syndrome 125250 AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.1220 ACTB Melanie Marty reviewed gene: ACTB: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29220674; Phenotypes: ?Dystonia, juvenile-onset 607371, Baraitser-Winter syndrome 1 243310, ACTB-related neurodevelopment disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.1218 NDUFA12 Zornitza Stark Mode of inheritance for gene: NDUFA12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1216 NDUFA12 Zornitza Stark reviewed gene: NDUFA12: Rating: RED; Mode of pathogenicity: None; Publications: 21617257; Phenotypes: Mitochondrial complex I deficiency, nuclear type 23 618244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1214 MRPS7 Zornitza Stark Mode of inheritance for gene: MRPS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1212 MRPS7 Zornitza Stark reviewed gene: MRPS7: Rating: RED; Mode of pathogenicity: None; Publications: 25556185; Phenotypes: Combined oxidative phosphorylation deficiency 34, MIM# 617872; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1210 MRPS23 Zornitza Stark Mode of inheritance for gene: MRPS23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1208 MRPS23 Zornitza Stark reviewed gene: MRPS23: Rating: RED; Mode of pathogenicity: None; Publications: 26741492; Phenotypes: Hepatic disease, Combined respiratory chain complex deficiencies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1208 MRPL12 Zornitza Stark Mode of inheritance for gene: MRPL12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1204 MRPL12 Zornitza Stark reviewed gene: MRPL12: Rating: RED; Mode of pathogenicity: None; Publications: 23603806; Phenotypes: Growth retardation, neurological deterioration, mitochondrial translation deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1202 LYRM4 Zornitza Stark Mode of inheritance for gene: LYRM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1200 LYRM4 Zornitza Stark reviewed gene: LYRM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 23814038, 31497476; Phenotypes: Combined oxidative phosphorylation deficiency 19, MIM# 615595; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1198 COX8A Zornitza Stark Mode of inheritance for gene: COX8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1196 COX8A Zornitza Stark reviewed gene: COX8A: Rating: RED; Mode of pathogenicity: None; Publications: 26685157; Phenotypes: Mitochondrial complex IV deficiency, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1194 COA5 Zornitza Stark Mode of inheritance for gene: COA5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1192 COA5 Zornitza Stark reviewed gene: COA5: Rating: RED; Mode of pathogenicity: None; Publications: 21457908; Phenotypes: Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3, MIM# 616500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1191 CLCN5 Zornitza Stark Mode of inheritance for gene: CLCN5 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1190 CLCN5 Zornitza Stark reviewed gene: CLCN5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dent disease, MIM#300009, Hypophosphatemic rickets, MIM#300554, Nephrolithiasis, type I, MIM#310468, Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, MIM#308990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1189 PHEX Zornitza Stark Mode of inheritance for gene: PHEX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1188 PHEX Zornitza Stark reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypophosphatemic rickets, MIM#307800; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1186 EHMT1 Zornitza Stark Mode of inheritance for gene: EHMT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1185 EHMT1 Crystle Lee reviewed gene: EHMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19264732; Phenotypes: Kleefstra syndrome 1 (MIM#610253); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1183 FIBP Zornitza Stark Mode of inheritance for gene: FIBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1181 FIBP Zornitza Stark reviewed gene: FIBP: Rating: AMBER; Mode of pathogenicity: None; Publications: 26660953, 27183861; Phenotypes: Thauvin-Robinet-Faivre syndrome, MIM#617107; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1179 CHST8 Zornitza Stark Mode of inheritance for gene: CHST8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1177 CHST8 Zornitza Stark reviewed gene: CHST8: Rating: RED; Mode of pathogenicity: None; Publications: 22289416, 28204496; Phenotypes: Peeling skin syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1177 RASA2 Sebastian Lunke Mode of inheritance for gene: RASA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1175 RASA2 Sebastian Lunke reviewed gene: RASA2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25049390, 30311384; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1174 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Literature
Mendeliome v0.1172 RALGAPA1 Zornitza Stark gene: RALGAPA1 was added
gene: RALGAPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RALGAPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RALGAPA1 were set to 32004447
Phenotypes for gene: RALGAPA1 were set to Intellectual disability; hypotonia; infantile spasms.
Review for gene: RALGAPA1 was set to GREEN
Added comment: Four unrelated individuals reported.
Sources: Literature
Mendeliome v0.1171 EPB41L1 Zornitza Stark Phenotypes for gene: EPB41L1 were changed from to Mental retardation, autosomal dominant 11, MIM# 614257
Mendeliome v0.1169 EPB41L1 Zornitza Stark Mode of inheritance for gene: EPB41L1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1167 EPB41L1 Zornitza Stark reviewed gene: EPB41L1: Rating: RED; Mode of pathogenicity: None; Publications: 21376300, 26539891, 25961944; Phenotypes: Mental retardation, autosomal dominant 11, MIM# 614257; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1165 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1164 EMC1 Zornitza Stark reviewed gene: EMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26942288, 29271071; Phenotypes: Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1163 SOD2 Zornitza Stark Mode of inheritance for gene: SOD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1161 SOD2 Zornitza Stark reviewed gene: SOD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Microvascular complications of diabetes 6} 612634; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1159 ATAD3A Zornitza Stark Mode of inheritance for gene: ATAD3A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1158 ATAD3A Zornitza Stark reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27640307, 32004445; Phenotypes: Harel-Yoon syndrome, MIM# 617183; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1156 MYOM1 Zornitza Stark Mode of inheritance for gene: MYOM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1154 MYOM1 Zornitza Stark reviewed gene: MYOM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27600940, 26656175, 21256114; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1152 DLG4 Zornitza Stark Mode of inheritance for gene: DLG4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1150 DLG4 Zornitza Stark edited their review of gene: DLG4: Added comment: Four unrelated individuals reported.; Changed rating: GREEN; Changed publications: 27479843, 25123844, 19617690, 29460436, 23020937, 28135719; Changed phenotypes: Intellectual disability, Marfanoid habitus; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes
Mendeliome v0.1147 DIP2B Zornitza Stark Mode of inheritance for gene: DIP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1145 DIP2B Zornitza Stark reviewed gene: DIP2B: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17236128; Phenotypes: Mental retardation, FRA12A type, MIM# 136630; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1144 DCPS Zornitza Stark gene: DCPS was added
gene: DCPS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DCPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCPS were set to 25701870; 30289615; 25712129
Phenotypes for gene: DCPS were set to Al-Raqad syndrome, MIM#616459
Review for gene: DCPS was set to GREEN
gene: DCPS was marked as current diagnostic
Added comment: 7 individuals from 3 families reported.
Sources: Expert list
Mendeliome v0.1142 CUX1 Zornitza Stark gene: CUX1 was added
gene: CUX1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUX1 were set to 25059644; 20510857; 30014507
Phenotypes for gene: CUX1 were set to Global developmental delay with or without impaired intellectual development, 618330
Review for gene: CUX1 was set to GREEN
gene: CUX1 was marked as current diagnostic
Added comment: Nine individuals from 7 families reported. Three individuals had normal intelligence at school age despite significant early developmental delay.
Sources: Expert list
Mendeliome v0.1139 COA3 Zornitza Stark Mode of inheritance for gene: COA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1137 COA3 Zornitza Stark reviewed gene: COA3: Rating: RED; Mode of pathogenicity: None; Publications: 25604084; Phenotypes: Mitochondrial complex IV deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1135 CNTN3 Zornitza Stark Mode of inheritance for gene: CNTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1133 CNTN3 Zornitza Stark reviewed gene: CNTN3: Rating: RED; Mode of pathogenicity: None; Publications: 28600779; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1133 CDK5R1 Zornitza Stark Mode of inheritance for gene: CDK5R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1129 CDK5R1 Zornitza Stark reviewed gene: CDK5R1: Rating: RED; Mode of pathogenicity: None; Publications: 30733659; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1129 LIPN Zornitza Stark Phenotypes for gene: LIPN were changed from to Ichthyosis, congenital, autosomal recessive 8, MIM# 613943
Mendeliome v0.1127 LIPN Zornitza Stark Mode of inheritance for gene: LIPN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1125 LIPN Zornitza Stark reviewed gene: LIPN: Rating: RED; Mode of pathogenicity: None; Publications: 21439540; Phenotypes: Ichthyosis, congenital, autosomal recessive 8, MIM# 613943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1124 SDR9C7 Zornitza Stark gene: SDR9C7 was added
gene: SDR9C7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SDR9C7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SDR9C7 were set to 28173123; 28369735
Phenotypes for gene: SDR9C7 were set to Ichthyosis, congenital, autosomal recessive 13 MIM#617574
Review for gene: SDR9C7 was set to GREEN
Added comment: Three homozygous variants in 4 families with congenital ichthyosis.
Sources: Expert list
Mendeliome v0.1121 ACSL4 Zornitza Stark Mode of inheritance for gene: ACSL4 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1120 ACSL4 Zornitza Stark reviewed gene: ACSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11889465, 12525535; Phenotypes: Mental retardation, X-linked 63, MIM# 300387 XLD; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1117 RBBP8 Zornitza Stark Mode of inheritance for gene: RBBP8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1115 NIPBL Zornitza Stark Mode of inheritance for gene: NIPBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1112 HUWE1 Zornitza Stark Mode of inheritance for gene: HUWE1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1109 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1108 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from to Cranioectodermal dysplasia 2, MIM#613610; Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091
Mendeliome v0.1107 WDR35 Zornitza Stark Mode of inheritance for gene: WDR35 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1105 DNAH11 Zornitza Stark Mode of inheritance for gene: DNAH11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1103 ELOVL1 Zornitza Stark Mode of inheritance for gene: ELOVL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1102 ELOVL1 Zornitza Stark reviewed gene: ELOVL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies MIM#618527; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1102 CLDN10 Zornitza Stark Phenotypes for gene: CLDN10 were changed from to HELIX syndrome MIM#617671; hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX)
Mendeliome v0.1101 CLDN10 Zornitza Stark Mode of inheritance for gene: CLDN10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1100 CLDN10 Zornitza Stark reviewed gene: CLDN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: HELIX syndrome MIM#617671, hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1096 CSTA Zornitza Stark Mode of inheritance for gene: CSTA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1095 CSTA Zornitza Stark reviewed gene: CSTA: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944047, 23534700, 25400170; Phenotypes: Peeling skin syndrome 4 MIM#607936, exfoliative ichthyosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1093 CDSN Zornitza Stark Mode of inheritance for gene: CDSN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1092 CDSN Zornitza Stark reviewed gene: CDSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24794518, 18436651, 20691404, 21191406; Phenotypes: Peeling skin syndrome 1 MIM#270300, ichthyosiform erythroderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1091 CASP14 Zornitza Stark gene: CASP14 was added
gene: CASP14 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CASP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP14 were set to 27494380; 23014340; 17515931
Phenotypes for gene: CASP14 were set to Ichthyosis, congenital, autosomal recessive 12 MIM#617320
Review for gene: CASP14 was set to AMBER
Added comment: The same 2bp deletion was identified in 3 patients with a mild form of generalised ichthyosis from 2 Algerian families. Casp14-/- mouse models had prominent dermatological features.
Sources: Expert Review
Mendeliome v0.1087 ALDH3A2 Zornitza Stark Mode of inheritance for gene: ALDH3A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1086 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31273323; Phenotypes: Sjogren-Larsson syndrome MIM#270200, spasticity, ichthyosis, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1084 ABHD5 Zornitza Stark Mode of inheritance for gene: ABHD5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1083 ABHD5 Zornitza Stark reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome MIM#275630, neutral lipid storage disease with ichthyosis, non-bullous congenital ichthyosiform erithroderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1083 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270
Mendeliome v0.1081 TUBGCP6 Zornitza Stark Mode of inheritance for gene: TUBGCP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1080 TUBGCP6 Zornitza Stark reviewed gene: TUBGCP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25344692, 22279524; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1080 MYT1L Zornitza Stark Phenotypes for gene: MYT1L were changed from to Mental retardation, autosomal dominant 39, MIM# 616521
Mendeliome v0.1078 MYT1L Zornitza Stark Mode of inheritance for gene: MYT1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1077 MYT1L Zornitza Stark reviewed gene: MYT1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 28859103; Phenotypes: Mental retardation, autosomal dominant 39, MIM# 616521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1076 LIPT1 Zornitza Stark Mode of inheritance for gene: LIPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1074 ARSA Zornitza Stark Mode of inheritance for gene: ARSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1073 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from Myopathy, actin, congenital, with cores; Myopathy, actin, congenital, with excess of thin myofilaments; Myopathy, congenital, with fiber-type disproportion 1; Nemaline myopathy 3; ?Myopathy, scapulohumeroperoneal to Myopathy, actin, congenital, with cores, MIM#161800; Myopathy, actin, congenital, with excess of thin myofilaments, MIM#161800; Myopathy, congenital, with fiber-type disproportion 1, MIM#255310; Nemaline myopathy 3, MIM#161800; ?Myopathy, scapulohumeroperoneal
Mendeliome v0.1072 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from to Myopathy, actin, congenital, with cores; Myopathy, actin, congenital, with excess of thin myofilaments; Myopathy, congenital, with fiber-type disproportion 1; Nemaline myopathy 3; ?Myopathy, scapulohumeroperoneal
Mendeliome v0.1070 ACTA1 Zornitza Stark Mode of inheritance for gene: ACTA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1069 RBBP8 Elena Savva reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21998596; Phenotypes: Jawad syndrome, Seckel syndrome 2, Pancreatic carcinoma, somatic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1069 NIPBL Elena Savva reviewed gene: NIPBL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1069 HUWE1 Elena Savva reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30797980, 29180823; Phenotypes: Mental retardation, X-linked syndromic, Turner type, Say-Meyer syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1069 FLNA Elena Savva reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30089473; Phenotypes: ?FG syndrome 2, XL, Cardiac valvular dysplasia, X-linked, Congenital short bowel syndrome, Frontometaphyseal dysplasia 1, Heterotopia, periventricular, 1, Intestinal pseudoobstruction, neuronal Melnick-Needles syndrome, Otopalatodigital syndrome, type I, Otopalatodigital syndrome, type II, Terminal osseous dysplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1069 LIPE Kristin Rigbye gene: LIPE was added
gene: LIPE was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: LIPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPE were set to 27862896; 25475467; 24848981
Phenotypes for gene: LIPE were set to Lipodystrophy, familial partial, type 6, 615980
Review for gene: LIPE was set to GREEN
gene: LIPE was marked as current diagnostic
Added comment: LIPE is confirmed to be associated with partial familial lipodystrophy in OMIM.
There are 3 unrelated cases of patients with partial lipodystrophy with different loss of function variants in the LIPE gene.
Sources: Expert list
Mendeliome v0.1069 WDR35 Elena Savva reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cranioectodermal dysplasia 2, Short-rib thoracic dysplasia 7 with or without polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1069 DNAH11 Elena Savva reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1067 FGF3 Zornitza Stark Mode of inheritance for gene: FGF3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1066 IRF2BPL Zornitza Stark Phenotypes for gene: IRF2BPL were changed from to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM#618088
Mendeliome v0.1064 IRF2BPL Zornitza Stark Mode of inheritance for gene: IRF2BPL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1060 PHF8 Zornitza Stark Mode of inheritance for gene: PHF8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1059 PHF8 Zornitza Stark reviewed gene: PHF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17661819, 17594395, 16199551; Phenotypes: Mental retardation syndrome, X-linked, Siderius type, MIM#300263; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1056 LONP1 Zornitza Stark Mode of inheritance for gene: LONP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1055 IARS Zornitza Stark Mode of inheritance for gene: IARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 IARS Zornitza Stark reviewed gene: IARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27426735; Phenotypes: Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 LIPT1 Elena Savva reviewed gene: LIPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoyltransferase 1 deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 ARSA Elena Savva reviewed gene: ARSA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Metachromatic leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 ACTA1 Elena Savva reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19562689, 15236405; Phenotypes: Myopathy, actin, congenital, with cores, Myopathy, actin, congenital, with excess of thin myofilaments, Myopathy, congenital, with fiber-type disproportion 1, Nemaline myopathy 3, ?Myopathy, scapulohumeroperoneal; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1054 FGF3 Elena Savva reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1054 IRF2BPL Elena Savva reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30057031; Phenotypes: Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.1054 KMT5B Zornitza Stark Phenotypes for gene: KMT5B were changed from to Mental retardation, autosomal dominant 51
Mendeliome v0.1053 KMT5B Zornitza Stark Mode of inheritance for gene: KMT5B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1050 KMT5B Elena Savva reviewed gene: KMT5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 51; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.1050 LONP1 Elena Savva reviewed gene: LONP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31636596; Phenotypes: CODAS syndrome, Mitochondrial cytopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1049 GNAO1 Zornitza Stark Mode of inheritance for gene: GNAO1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1048 GNAO1 Zornitza Stark reviewed gene: GNAO1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28747448, 30682224; Phenotypes: Epileptic encephalopathy, early infantile, 17, Neurodevelopmental disorder with involuntary movements; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1048 CACNG2 Zornitza Stark Phenotypes for gene: CACNG2 were changed from to Mental retardation, autosomal dominant 10, MIM#614256
Mendeliome v0.1045 CACNG2 Zornitza Stark reviewed gene: CACNG2: Rating: RED; Mode of pathogenicity: None; Publications: 21376300; Phenotypes: Mental retardation, autosomal dominant 10, MIM#614256; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1043 PPM1D Zornitza Stark Mode of inheritance for gene: PPM1D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1042 PPM1D Zornitza Stark reviewed gene: PPM1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 28343630, 31916397, 30795918, 29758292; Phenotypes: Jansen de Vries syndrome, MIM #617450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1040 EGFR Zornitza Stark Mode of inheritance for gene: EGFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1038 EGFR Zornitza Stark reviewed gene: EGFR: Rating: RED; Mode of pathogenicity: None; Publications: 24691054; Phenotypes: Inflammatory skin and bowel disease, neonatal, 2, OMIM # 616069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1032 SLC9A3R1 Zornitza Stark Mode of inheritance for gene: SLC9A3R1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1030 SLC9A3R1 Zornitza Stark reviewed gene: SLC9A3R1: Rating: RED; Mode of pathogenicity: None; Publications: 18784102; Phenotypes: Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM# 612287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.1030 EGF Zornitza Stark Mode of inheritance for gene: EGF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1026 EGF Zornitza Stark reviewed gene: EGF: Rating: RED; Mode of pathogenicity: None; Publications: 17671655; Phenotypes: Hypomagnesemia 4, renal, MIM#611718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1025 MYRF Zornitza Stark gene: MYRF was added
gene: MYRF was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYRF were set to 31048900; 31172260; 31266062; 31700225
Phenotypes for gene: MYRF were set to Nanophthalmos; High hyperopia
Review for gene: MYRF was set to GREEN
gene: MYRF was marked as current diagnostic
Added comment: Multiple affected individuals reported.
Sources: Expert list
Mendeliome v0.1023 FBXW11 Alison Yeung gene: FBXW11 was added
gene: FBXW11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBXW11 were set to PMID: 31402090
Phenotypes for gene: FBXW11 were set to Intellectual disability; developmental eye anomalies; digital anomalies
Review for gene: FBXW11 was set to GREEN
Added comment: Reported in >3 unrelated individuals
Functional studies in zebrafish
Sources: Literature
Mendeliome v0.1022 ANAPC1 Alison Yeung Mode of inheritance for gene ANAPC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1020 ANAPC1 Alison Yeung gene: ANAPC1 was added
gene: ANAPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANAPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ANAPC1 were set to PMID: 31303264
Phenotypes for gene: ANAPC1 were set to Rothmund Thomson syndrome type 1, OMIM 618625
Review for gene: ANAPC1 was set to GREEN
gene: ANAPC1 was marked as current diagnostic
Added comment: 7 unrelated families reported
Sources: Literature
Mendeliome v0.1018 RINT1 Alison Yeung gene: RINT1 was added
gene: RINT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to PMID: 31204009
Phenotypes for gene: RINT1 were set to Recurrent acute liver failure
Review for gene: RINT1 was set to GREEN
gene: RINT1 was marked as current diagnostic
Added comment: three unrelated individuals reported
Sources: Literature
Mendeliome v0.1016 MAB21L1 Sue White gene: MAB21L1 was added
gene: MAB21L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 30487245
Phenotypes for gene: MAB21L1 were set to Cerebellar, ocular, craniofacial, and genital syndrome #MIM 618479
Penetrance for gene: MAB21L1 were set to Complete
Review for gene: MAB21L1 was set to GREEN
Added comment: Sources: Literature
Mendeliome v0.1012 ARHGEF6 Zornitza Stark Mode of inheritance for gene: ARHGEF6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1010 ARHGEF6 Zornitza Stark reviewed gene: ARHGEF6: Rating: RED; Mode of pathogenicity: None; Publications: 11017088; Phenotypes: MENTAL RETARDATION X-LINKED TYPE 46; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.1008 XRCC4 Zornitza Stark Mode of inheritance for gene: XRCC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1007 XRCC4 Crystle Lee reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25839420, 25728776; Phenotypes: Short stature, microcephaly, and endocrine dysfunction (MIM#616541); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1006 ANK3 Zornitza Stark Phenotypes for gene: ANK3 were changed from to Mental retardation, autosomal recessive, 37, MIM# 615493
Mendeliome v0.1004 ANK3 Zornitza Stark Mode of inheritance for gene: ANK3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1002 ANK3 Zornitza Stark reviewed gene: ANK3: Rating: RED; Mode of pathogenicity: None; Publications: 23390136, 28687526; Phenotypes: Mental retardation, autosomal recessive, 37 615493; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark gene: ATP6V1C2 was added
gene: ATP6V1C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V1C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1C2 were set to 31959358
Phenotypes for gene: ATP6V1C2 were set to Distal renal tubular acidosis
Review for gene: ATP6V1C2 was set to RED
Added comment: Single family reported, limited functional data.
Sources: Literature
Mendeliome v0.998 ANKRD11 Zornitza Stark Mode of inheritance for gene: ANKRD11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.996 ANKRD11 Ain Roesley reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31191201, 31337854; Phenotypes: KBG syndrome (MIM # 148050); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.994 HCN2 Zornitza Stark Mode of inheritance for gene: HCN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.992 HCN2 Zornitza Stark edited their review of gene: HCN2: Added comment: Further cases identified. Evidence for both mono-allelic and bi-allelic variants causing disease; also evidence for both GoF and LoF as mechanism.; Changed rating: GREEN; Changed publications: 22131395, 30986657, 29064616, 20437590, 12514127, 17931874; Changed phenotypes: Genetic epilepsy with febrile seizures plus, Other seizure disorders; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.991 CTBP1 Zornitza Stark gene: CTBP1 was added
gene: CTBP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, MIM#617915
Review for gene: CTBP1 was set to GREEN
gene: CTBP1 was marked as current diagnostic
Added comment: At least 12 unrelated individuals reported with this neurodevelopmental disorder.
Sources: Expert list
Mendeliome v0.989 AGO1 Zornitza Stark gene: AGO1 was added
gene: AGO1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO1 were set to 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719
Phenotypes for gene: AGO1 were set to Intellectual disability; autism
Review for gene: AGO1 was set to GREEN
Added comment: Multiple individuals reported with de novo variants in this gene, most as part of large ID cohorts so phenotypic information is scarce; however, given large number I have rated as Green.
Sources: Expert list
Mendeliome v0.987 CNOT2 Sebastian Lunke gene: CNOT2 was added
gene: CNOT2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608
Review for gene: CNOT2 was set to GREEN
gene: CNOT2 was marked as current diagnostic
Added comment: From GEL: Three independent patients with non-sense or intra-genic deletions
Sources: Expert list
Mendeliome v0.986 CCDC88C Sebastian Lunke Phenotypes for gene: CCDC88C were changed from Spinocerebellar ataxia 40, MIM#616053 to Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR
Mendeliome v0.984 CCDC88C Sebastian Lunke Mode of inheritance for gene: CCDC88C was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.982 CCDC88C Sebastian Lunke reviewed gene: CCDC88C: Rating: GREEN; Mode of pathogenicity: None; Publications: 23042809, 21031079, 25062847, 30398676; Phenotypes: Spinocerebellar ataxia 40, MIM#616053, Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.981 CCDC47 Sebastian Lunke gene: CCDC47 was added
gene: CCDC47 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CCDC47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC47 were set to 30401460
Phenotypes for gene: CCDC47 were set to Trichohepatoneurodevelopmental syndrome, 618268
Review for gene: CCDC47 was set to GREEN
gene: CCDC47 was marked as current diagnostic
Added comment: From GEL: Morimoto el al. (PMID: 30401460) report on 4 individuals from 4 unrelated families with biallelic LoF variants in CCDC47. The phenotype consisted of abnormal (woolly) hair, liver dysfunction, common facial features as well as DD/ID
Sources: Expert list
Mendeliome v0.980 CLIC2 Zornitza Stark Mode of inheritance for gene: CLIC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.976 CLIC2 Zornitza Stark reviewed gene: CLIC2: Rating: RED; Mode of pathogenicity: None; Publications: 22814392, 25927380; Phenotypes: Mental retardation, X-linked, syndromic 32, 300886; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.975 IKZF5 Zornitza Stark gene: IKZF5 was added
gene: IKZF5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IKZF5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF5 were set to 31217188
Phenotypes for gene: IKZF5 were set to Thrombocytopaenia
Review for gene: IKZF5 was set to GREEN
Added comment: Five unrelated individuals with missense variants in this gene. Two de novo, three segregated with disease
Sources: Expert Review
Mendeliome v0.973 TTC12 Zornitza Stark gene: TTC12 was added
gene: TTC12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC12 were set to 31978331
Phenotypes for gene: TTC12 were set to Ciliary dyskinesia
Review for gene: TTC12 was set to GREEN
Added comment: Four unrelated families reported, LoF variants, respiratory phenotype.
Sources: Literature
Mendeliome v0.970 GCSH Zornitza Stark Mode of inheritance for gene: GCSH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.968 GCSH Zornitza Stark reviewed gene: GCSH: Rating: RED; Mode of pathogenicity: None; Publications: 1671321; Phenotypes: Glycine encephalopathy, MIM# 605899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.967 STT3B Zornitza Stark Mode of inheritance for gene: STT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.963 STT3B Zornitza Stark reviewed gene: STT3B: Rating: RED; Mode of pathogenicity: None; Publications: 23842455; Phenotypes: Congenital disorder of glycosylation, type Ix 615597; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.961 SLC39A8 Zornitza Stark Mode of inheritance for gene: SLC39A8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.959 PIGS Zornitza Stark gene: PIGS was added
gene: PIGS was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18 618143
Review for gene: PIGS was set to GREEN
Added comment: Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to ID/EE
Sources: Expert Review
Mendeliome v0.957 FUK Zornitza Stark gene: FUK was added
gene: FUK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUK were set to 30503518
Phenotypes for gene: FUK were set to Congenital disorder of glycosylation with defective fucosylation 2, MIM# 618324
Review for gene: FUK was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Literature
Mendeliome v0.955 ZNF142 Zornitza Stark gene: ZNF142 was added
gene: ZNF142 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF142 were set to 31036918
Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM#618425
Review for gene: ZNF142 was set to GREEN
gene: ZNF142 was marked as current diagnostic
Added comment: 7 individuals from 4 unrelated families reported.
Sources: Expert list
Mendeliome v0.953 RALA Zornitza Stark gene: RALA was added
gene: RALA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RALA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RALA were set to 30500825
Phenotypes for gene: RALA were set to Intellectual disability; Seizures
Review for gene: RALA was set to GREEN
gene: RALA was marked as current diagnostic
Added comment: 11 individuals from 10 unrelated families reported with this neurodevelopmental syndrome, half had seizures.
Sources: Expert list
Mendeliome v0.951 NBEA Zornitza Stark gene: NBEA was added
gene: NBEA was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NBEA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NBEA were set to 30269351; 28554332; 12746398; 12826745; 11450821; 3377648; 23277425; 22109531; 23153818
Phenotypes for gene: NBEA were set to Intellectual disability; Seizures
Review for gene: NBEA was set to GREEN
gene: NBEA was marked as current diagnostic
Added comment: 24 de novo variants reported in individuals with a neurodevelopmental disorder
Sources: Expert list
Mendeliome v0.949 MACF1 Zornitza Stark gene: MACF1 was added
gene: MACF1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACF1 were set to 30471716
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, MIM# 618325
Mode of pathogenicity for gene: MACF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MACF1 was set to GREEN
Added comment: Nine individuals (including a pair of twins) reported with de novo variants in this gene.
Sources: Expert list
Mendeliome v0.945 KATNB1 Zornitza Stark Mode of inheritance for gene: KATNB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.942 NLGN4X Zornitza Stark Mode of inheritance for gene: NLGN4X was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.940 NLGN4X Zornitza Stark reviewed gene: NLGN4X: Rating: RED; Mode of pathogenicity: None; Publications: 12669065, 18231125, 10071191, 29428674; Phenotypes: Mental retardation, X-linked, MIM# 300495; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.939 HNRNPR Zornitza Stark gene: HNRNPR was added
gene: HNRNPR was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HNRNPR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPR were set to 26795593; 31079900
Phenotypes for gene: HNRNPR were set to Intellectual disability; seizures
Review for gene: HNRNPR was set to GREEN
gene: HNRNPR was marked as current diagnostic
Added comment: Five unrelated individuals reported with de novo variants and a neurodevelopmental disorder.
Sources: Expert list
Mendeliome v0.936 USB1 Zornitza Stark Mode of inheritance for gene: USB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.935 USB1 Ain Roesley reviewed gene: USB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25044170, 27612988; Phenotypes: Poikiloderma with neutropenia (OMIM #604173); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.933 GNB5 Zornitza Stark Mode of inheritance for gene: GNB5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.931 FAR1 Zornitza Stark Phenotypes for gene: FAR1 were changed from to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154
Mendeliome v0.930 FAR1 Zornitza Stark Mode of inheritance for gene: FAR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.928 FAR1 Zornitza Stark reviewed gene: FAR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25439727; Phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.926 EFHC1 Zornitza Stark Mode of inheritance for gene: EFHC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.923 CEP89 Zornitza Stark Mode of inheritance for gene: CEP89 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.918 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.914 RAB11A Zornitza Stark gene: RAB11A was added
gene: RAB11A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB11A were set to 29100083
Phenotypes for gene: RAB11A were set to Intellectual disability; seizures
Review for gene: RAB11A was set to AMBER
Added comment: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated.
Sources: Literature
Mendeliome v0.913 RAB11B Zornitza Stark reviewed gene: RAB11B: Rating: AMBER; Mode of pathogenicity: None; Publications: 29100083; Phenotypes: Intellectual disability, seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.913 NAGA Ain Roesley reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11313741, 31468281; Phenotypes: Kanzaki disease (MIM # 609242), Schindler disease, type I or III (MIM# 609241); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.912 DHPS Zornitza Stark gene: DHPS was added
gene: DHPS was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to 30661771
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment, MIM#618480
Review for gene: DHPS was set to GREEN
gene: DHPS was marked as current diagnostic
Added comment: 5 individuals from 4 unrelated families with biallelic pathogenic variants in DHPS, note one variant is recurrent (c.518A>G or p.Asn173Ser). The phenotype consisted of DD/ID (5/5), tone abnormalities (hypotonia/hypertonia/spasticity - 5/5), seizures (5/5 - in one case though unclear staring spells) with EEG abnormalities (5/5). Additionally most individuals displayed behavioral issues, or some common facial features
Sources: Expert list
Mendeliome v0.911 RBFOX1 Zornitza Stark Mode of inheritance for gene: RBFOX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.907 RBFOX1 Zornitza Stark reviewed gene: RBFOX1: Rating: RED; Mode of pathogenicity: None; Publications: 24664471; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.905 DDOST Zornitza Stark Mode of inheritance for gene: DDOST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.903 DDOST Zornitza Stark reviewed gene: DDOST: Rating: AMBER; Mode of pathogenicity: None; Publications: 22305527; Phenotypes: Congenital disorder of glycosylation, type Ir, MIM# 614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.903 PIK3C2A Zornitza Stark Mode of inheritance for gene: PIK3C2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.901 PIK3C2A Zornitza Stark gene: PIK3C2A was added
gene: PIK3C2A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2A were set to 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, MIM# 618440
Review for gene: PIK3C2A was set to GREEN
gene: PIK3C2A was marked as current diagnostic
Added comment: Three unrelated consanguineous families reported.
Sources: Expert list
Mendeliome v0.899 FGF16 Zornitza Stark gene: FGF16 was added
gene: FGF16 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FGF16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FGF16 were set to Metacarpal 4-5 fusion, MIM# 309630
Review for gene: FGF16 was set to GREEN
gene: FGF16 was marked as current diagnostic
Added comment: Sources: Expert list
Mendeliome v0.897 GAS1 Zornitza Stark Mode of inheritance for gene: GAS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.893 GAS1 Zornitza Stark reviewed gene: GAS1: Rating: RED; Mode of pathogenicity: None; Publications: 21842183, 20583177; Phenotypes: Holoprosencephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.891 IMMP2L Zornitza Stark Mode of inheritance for gene: IMMP2L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.889 IMMP2L Zornitza Stark reviewed gene: IMMP2L: Rating: RED; Mode of pathogenicity: None; Publications: 29788020, 29152845; Phenotypes: Autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.888 MTHFS Zornitza Stark gene: MTHFS was added
gene: MTHFS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Review for gene: MTHFS was set to GREEN
Added comment: Three unrelated individuals reported with supporting biochemical evidence.
Sources: Literature
Mendeliome v0.885 HOXB6 Zornitza Stark Mode of inheritance for gene: HOXB6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.883 LIFR Zornitza Stark Mode of inheritance for gene: LIFR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.881 LIFR Zornitza Stark Mode of inheritance for gene: LIFR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.878 CACNA1B Zornitza Stark Mode of inheritance for gene: CACNA1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.877 CACNA1B Zornitza Stark reviewed gene: CACNA1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30982612; Phenotypes: Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, MIM# 618497; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.876 CDH2 Zornitza Stark gene: CDH2 was added
gene: CDH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDH2 were set to 31585109
Phenotypes for gene: CDH2 were set to Intellectual disability; corpus callosum abnormalities; congenital abnormalities
Review for gene: CDH2 was set to GREEN
Added comment: Nine unrelated individuals reported with de novo variants in this gene.
Sources: Literature
Mendeliome v0.875 NTNG2 Zornitza Stark Phenotypes for gene: NTNG2 were changed from Intellectual disability; autism; dysmorphic features to Intellectual disability; autism; dysmorphic features; Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Mendeliome v0.872 NTNG2 Zornitza Stark Mode of inheritance for gene: NTNG2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.871 NTNG2 Zornitza Stark reviewed gene: NTNG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31668703; Phenotypes: Intellectual disability, autism, dysmorphic features; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.870 RPL13 Zornitza Stark gene: RPL13 was added
gene: RPL13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL13 were set to 31630789
Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal Dysplasia with Severe Short Stature
Review for gene: RPL13 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants.
Sources: Literature
Mendeliome v0.867 FOXJ1 Zornitza Stark Mode of inheritance for gene: FOXJ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.866 FOXJ1 Zornitza Stark reviewed gene: FOXJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31630787; Phenotypes: hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.865 TUBGCP2 Zornitza Stark gene: TUBGCP2 was added
gene: TUBGCP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to 31630790
Phenotypes for gene: TUBGCP2 were set to Lissencephaly; pachygyria; subcortical band heterotopia; microcephaly; intellectual disability
Review for gene: TUBGCP2 was set to GREEN
Added comment: Four unrelated families reported.
Sources: Literature
Mendeliome v0.862 RRAS2 Zornitza Stark Mode of inheritance for gene: RRAS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.861 RRAS2 Zornitza Stark reviewed gene: RRAS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31130282; Phenotypes: Noonan syndrome 12, OMIM #618624; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.860 TP73 Alison Yeung gene: TP73 was added
gene: TP73 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP73 were set to PMID: 31130284
Phenotypes for gene: TP73 were set to Cortical malformation; Lissencephaly
Review for gene: TP73 was set to AMBER
Added comment: Two unrelated families reported. No functional data
Sources: Literature
Mendeliome v0.858 SMG8 Alison Yeung gene: SMG8 was added
gene: SMG8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMG8 were set to PMID: 31130284
Phenotypes for gene: SMG8 were set to Intellectual disability
Review for gene: SMG8 was set to AMBER
Added comment: Two unrelated families reported. No functional data
Sources: Literature
Mendeliome v0.856 IQSEC3 Alison Yeung gene: IQSEC3 was added
gene: IQSEC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQSEC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQSEC3 were set to PMID: 31130284
Phenotypes for gene: IQSEC3 were set to Intellectual disability
Review for gene: IQSEC3 was set to AMBER
Added comment: Two unrelated families reported, no functional data
Sources: Literature
Mendeliome v0.854 ICE1 Alison Yeung gene: ICE1 was added
gene: ICE1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ICE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICE1 were set to PMID: 31130284
Phenotypes for gene: ICE1 were set to Intellectual disability, cerebral atrophy
Review for gene: ICE1 was set to AMBER
Added comment: Two unrelated families reported, no functional data
Sources: Literature
Mendeliome v0.852 EIF2A Alison Yeung gene: EIF2A was added
gene: EIF2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF2A were set to PMID: 31130284
Phenotypes for gene: EIF2A were set to Intellectual disability, epilepsy
Review for gene: EIF2A was set to AMBER
Added comment: reported in two unrelated families
Sources: Literature
Mendeliome v0.844 KCNN3 Alison Yeung gene: KCNN3 was added
gene: KCNN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN3 were set to PMID: 31155282
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3; OMIM# 618658
Review for gene: KCNN3 was set to GREEN
gene: KCNN3 was marked as current diagnostic
Added comment: Three unrelated individuals reported
Sources: Literature
Mendeliome v0.841 CTNND2 Zornitza Stark Mode of inheritance for gene: CTNND2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.839 CTNND2 Zornitza Stark reviewed gene: CTNND2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25839933, 29127138, 25807484; Phenotypes: Intellectual disability, Autism, Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.837 CNOT1 Alison Yeung gene: CNOT1 was added
gene: CNOT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNOT1 were set to PMID: 31006513
Phenotypes for gene: CNOT1 were set to Holoprosencephaly 12, with or without pancreatic agenesis; OMIM# 618500
Review for gene: CNOT1 was set to GREEN
gene: CNOT1 was marked as current diagnostic
Added comment: Reported in 3 unrelated individuals
Sources: Literature
Mendeliome v0.835 IQSEC1 Zornitza Stark gene: IQSEC1 was added
gene: IQSEC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQSEC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQSEC1 were set to 31607425
Phenotypes for gene: IQSEC1 were set to Intellectual developmental disorder with short stature and behavioral abnormalities, MIM# 618687
Review for gene: IQSEC1 was set to GREEN
Added comment: Five individuals from two unrelated families reported, animal model data.
Sources: Literature
Mendeliome v0.833 ACAN Zornitza Stark gene: ACAN was added
gene: ACAN was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ACAN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ACAN were set to Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800; Spondyloepimetaphyseal dysplasia, aggrecan type 612813
Review for gene: ACAN was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.831 NKX2-2 Zornitza Stark gene: NKX2-2 was added
gene: NKX2-2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NKX2-2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NKX2-2 were set to 24411943; 9584121
Phenotypes for gene: NKX2-2 were set to Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment
Review for gene: NKX2-2 was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.830 GPC4 Alison Yeung reviewed gene: GPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30982611; Phenotypes: Keipert syndrome OMIM# 301026; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.828 LEMD2 Alison Yeung gene: LEMD2 was added
gene: LEMD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LEMD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LEMD2 were set to PMID: 30905398
Phenotypes for gene: LEMD2 were set to progeroid disorder
Review for gene: LEMD2 was set to AMBER
Added comment: two reported unrelated individuals, limited functional evidence
Sources: Literature
Mendeliome v0.825 PLD1 Zornitza Stark Mode of inheritance for gene: PLD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.822 FAM149B1 Alison Yeung gene: FAM149B1 was added
gene: FAM149B1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM149B1 were set to PMID: 30905400
Phenotypes for gene: FAM149B1 were set to Joubert; Ciliopathy
Review for gene: FAM149B1 was set to GREEN
gene: FAM149B1 was marked as current diagnostic
Added comment: Four unrelated families reported
Sources: Literature
Mendeliome v0.820 CARS Alison Yeung gene: CARS was added
gene: CARS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARS were set to PMID: 30824121
Phenotypes for gene: CARS were set to Intellectual disability; microcephaly; brittle hair and nails
Added comment: Three reported unrelated families
Sources: Literature
Mendeliome v0.818 MAPK8IP3 Zornitza Stark gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to 30612693
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431
Review for gene: MAPK8IP3 was set to GREEN
Added comment: >3 reported individuals and functional evidence in Caenorhabditis elegans
Sources: Literature
Mendeliome v0.816 NCAPG2 Zornitza Stark gene: NCAPG2 was added
gene: NCAPG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCAPG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPG2 were set to 30609410
Phenotypes for gene: NCAPG2 were set to Khan-Khan-Katsanis syndrome, MIM# 618460
Review for gene: NCAPG2 was set to GREEN
Added comment: Two families and functional evidence (zebrafish model).
Sources: Literature
Mendeliome v0.814 ADAMTS9 Zornitza Stark gene: ADAMTS9 was added
gene: ADAMTS9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS9 were set to 30609407
Phenotypes for gene: ADAMTS9 were set to Nephronophthisis-Related Ciliopathy
Review for gene: ADAMTS9 was set to GREEN
Added comment: Two families reported with functional evidence
Sources: Literature
Mendeliome v0.812 RIC1 Zornitza Stark gene: RIC1 was added
gene: RIC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIC1 were set to 31932796
Phenotypes for gene: RIC1 were set to Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Review for gene: RIC1 was set to AMBER
Added comment: Zebrafish model and consanguineous families but homozygous-by-descent.
Sources: Literature
Mendeliome v0.807 BNC2 Zornitza Stark gene: BNC2 was added
gene: BNC2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BNC2 were set to 31656805; 31051115
Phenotypes for gene: BNC2 were set to Lower urinary tract obstruction, congenital; OMIM #618612
Review for gene: BNC2 was set to GREEN
gene: BNC2 was marked as current diagnostic
Added comment: At least four unrelated families reported.
Sources: Expert list
Mendeliome v0.804 SIX2 Zornitza Stark Mode of inheritance for gene: SIX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.801 SRGAP1 Zornitza Stark Mode of inheritance for gene: SRGAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.797 TET3 Zornitza Stark gene: TET3 was added
gene: TET3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to 31928709
Phenotypes for gene: TET3 were set to Intellectual disability; dysmorphic features; abnormal growth; movement disorders
Review for gene: TET3 was set to GREEN
Added comment: Eleven individuals from 8 families described. Mono-allelic frameshift and nonsense variants occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity.
Sources: Literature
Mendeliome v0.793 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Review for gene: STN1 was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Expert list
Mendeliome v0.790 JAM2 Zornitza Stark gene: JAM2 was added
gene: JAM2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307
Phenotypes for gene: JAM2 were set to Primary brain calcification
Review for gene: JAM2 was set to GREEN
Added comment: Three unrelated families with bi-allelic variants reported. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages.
Sources: Literature
Mendeliome v0.788 TDP2 Zornitza Stark gene: TDP2 was added
gene: TDP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TDP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP2 were set to 31410782; 30109272; 24658003
Phenotypes for gene: TDP2 were set to Spinocerebellar ataxia, autosomal recessive 23; OMIM #616949
Review for gene: TDP2 was set to GREEN
Added comment: ID is part of the phenotype: 4 families with 6 affected patients, with functional evidence.

1 family with 3 affected sibs with homozygous splice site mutation in the TDP2 gene. Patient cell extracts showed absence of the full-length TDP2 protein and absence of 5-prime TDP activity, consistent with a loss of function, although 3-prime TDP activity, conferred by TDP1, was normal. In addition, patient lymphoblastoid cells were hypersensitive to the TOP2 poison etoposide. The findings indicated impaired capacity for double-strand break repair.

1 unrelated Egyptian patient with a similar disorder was homozygous for a truncating mutation in the TDP2 gene

1 unrelated Caucasian patient with same homozygous splice site mutation in the TDP2 gene. Western blot analysis did not detect TDP2 protein in patient primary skin fibroblasts. Patient fibroblasts showed an inability to rapidly repair topoisomerase-induced DNA double-strand breaks in the nucleus and also showed a profound hypersensitivity to this type of DNA damage. Complementation of patient cells with recombinant human TDP2 restored normal rates of nuclear DSB repair.
Sources: Expert list
Mendeliome v0.786 TRMT1 Zornitza Stark gene: TRMT1 was added
gene: TRMT1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TRMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT1 were set to 30289604; 26308914; 21937992
Phenotypes for gene: TRMT1 were set to Mental retardation, autosomal recessive 68; OMIM #618302
Review for gene: TRMT1 was set to GREEN
Added comment: 4 families reported:
-1 consanguineous Iranian family with 5 individuals with nonsyndromic moderate to severe impaired intellectual development.
-1 consanguineous Iranian family with 3 adult brothers with global developmental delay and moderately delayed intellectual development
-2 unrelated Pakistani families with 4 patients with impaired intellectual development.
All with homozygous mutations in the TRMT1 gene which segregated with the disorder in the families, but functional studies of the variants were not performed.
Sources: Expert list
Mendeliome v0.785 SLC35A3 Zornitza Stark Added comment: Comment when marking as ready: 1 family with 2 sibs, with segregation but no functional studies.

1 family with 8 affected people. The mutations segregated with the disorder in the family. Patient cells showed no normal transcript, indicating that they had no functional SLC35A3 protein. Golgi vesicles derived from patient fibroblasts showed significantly reduced transport of UDP-GlCNAc compared to controls.
Mendeliome v0.784 SLC35A3 Zornitza Stark Mode of inheritance for gene: SLC35A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.780 SLC9A7 Zornitza Stark gene: SLC9A7 was added
gene: SLC9A7 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SLC9A7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC9A7 were set to 30335141
Phenotypes for gene: SLC9A7 were set to Intellectual developmental disorder, X-linked 108; OMIM #301024
Review for gene: SLC9A7 was set to AMBER
Added comment: 6 males from 2 unrelated families with hemizygous missense mutation in the SLC9A7 gene. The mutation segregated with the disorder in the family. In vitro functional expression studies in CHO cells (AP-1 cells) showed that the mutation caused decreased levels of protein expression and reduced oligosaccharide maturation/glycosylation compared to wildtype, indicating impaired posttranslational processing. Subcellular localization studies indicated that protein trafficking was unaffected by the mutation. However, examination of the trans-Golgi compartment suggested a gain-of-function effect and a perturbation of glycosylation of secretory cargo. Serum transferrin studies in 1 patient suggested a glycosylation defect.
Sources: Literature
Mendeliome v0.778 KIAA1161 Zornitza Stark gene: KIAA1161 was added
gene: KIAA1161 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to 30656188; 30649222; 30460687; 29910000
Phenotypes for gene: KIAA1161 were set to Basal ganglia calcification, idiopathic, 7, autosomal recessive; OMIM #618317
Review for gene: KIAA1161 was set to GREEN
Added comment: Total 9 families, but no functional evidence:

12 patients from 6 unrelated Chinese families reported by Yao et al. (2018) and homozygous or compound heterozygous mutations in the MYORG gene. Functional studies of the variants and studies of patient cells were not performed, but the presence of nonsense mutations suggested a loss of function.

1 Chinese woman identified with homozygous nonsense mutation in the MYORG gene, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.

2 unrelated Middle Eastern families with homozygous mutations in the MYORG gene, which segregated with the disorder in the families. Functional studies of the variants were not performed.

4 sibs from one Turkish family with homozygous missense mutation in the MYORG gene, which segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.
Sources: Literature
Mendeliome v0.777 ZC3H14 Zornitza Stark Phenotypes for gene: ZC3H14 were changed from to Mental retardation, autosomal recessive 56; OMIM# 617125
Mendeliome v0.769 MDH1 Zornitza Stark gene: MDH1 was added
gene: MDH1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MDH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDH1 were set to 31538237
Phenotypes for gene: MDH1 were set to epilepsy; microcephaly; intellectual disability
Review for gene: MDH1 was set to AMBER
Added comment: single consanguinous family with biallelic missense variant in this gene and epilepsy, microcephaly, ID; some functional data.
Sources: Literature
Mendeliome v0.767 ISLR2 Zornitza Stark gene: ISLR2 was added
gene: ISLR2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ISLR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISLR2 were set to 30483960
Phenotypes for gene: ISLR2 were set to hydrocephalus; arthrogryposis; abdominal distension
Review for gene: ISLR2 was set to AMBER
Added comment: single consanguineous family with hydrocephalus and arthrogryposis and homozygous truncating variant, mouse model has hydrocephalus
Sources: Literature
Mendeliome v0.765 AGMO Sue White gene: AGMO was added
gene: AGMO was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905
Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy
Penetrance for gene: AGMO were set to Complete
Review for gene: AGMO was set to GREEN
Added comment: biallelic LOF and missense reported
Sources: Literature
Mendeliome v0.763 NOTCH2NL Sue White gene: NOTCH2NL was added
gene: NOTCH2NL was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NOTCH2NL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2NL were set to 31332381
Phenotypes for gene: NOTCH2NL were set to OMIM 603472 NEURONAL INTRANUCLEAR INCLUSION DISEASE; NIID
Penetrance for gene: NOTCH2NL were set to unknown
Mode of pathogenicity for gene: NOTCH2NL was set to Other
Review for gene: NOTCH2NL was set to GREEN
gene: NOTCH2NL was marked as current diagnostic
Added comment: adult onset neurodegenerative condition caused by STR expansion 5' of NOTCH2NL
Sources: Literature
Mendeliome v0.761 RFC1 Sue White gene: RFC1 was added
gene: RFC1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: RFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC1 were set to 30926972
Phenotypes for gene: RFC1 were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575
Penetrance for gene: RFC1 were set to unknown
Mode of pathogenicity for gene: RFC1 was set to Other
Review for gene: RFC1 was set to GREEN
Added comment: adult onset ataxia due to biallelic intronic STR expansion
Sources: Literature
Mendeliome v0.758 AVPR2 Zornitza Stark Mode of inheritance for gene: AVPR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.756 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAC were set to 21206088
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387
Review for gene: TRAC was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.755 NSMCE3 Zornitza Stark Mode of inheritance for gene: NSMCE3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.751 NSMCE3 Zornitza Stark reviewed gene: NSMCE3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27427983; Phenotypes: Lung disease, immunodeficiency, and chromosome breakage syndrome, MIM#617241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.750 MYSM1 Zornitza Stark gene: MYSM1 was added
gene: MYSM1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MYSM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYSM1 were set to 4288411; 28115216; 26220525
Phenotypes for gene: MYSM1 were set to Bone marrow failure syndrome 4, MIM#618116
Review for gene: MYSM1 was set to GREEN
Added comment: early-onset anaemia, leukopaenia, and decreased B cells, may have thrombocytopaenia or variable additional non-haematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay
Sources: Expert list
Mendeliome v0.749 AVPR2 Belinda Chong reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 9127330, PubMed: 15872203; Phenotypes: Diabetes insipidus, nephrogenic 304800, Nephrogenic syndrome of inappropriate antidiuresis 300539; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.748 STAG2 Zornitza Stark gene: STAG2 was added
gene: STAG2 was added to Mendeliome_VCGS. Sources: Other
Mode of inheritance for gene: STAG2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: STAG2 were set to 30765867; 28296084; 30447054; 29263825; 30158690
Phenotypes for gene: STAG2 were set to Mullegama-Klein-Martinez syndrome, MIM#301022
Review for gene: STAG2 was set to GREEN
Added comment: 12 unrelated families reported both males and females affected.
Sources: Other
Mendeliome v0.745 IRF3 Zornitza Stark Mode of inheritance for gene: IRF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.743 IRF3 Zornitza Stark reviewed gene: IRF3: Rating: AMBER; Mode of pathogenicity: None; Publications: 26513235; Phenotypes: {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 7}, MIM# 616532; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.742 MESD Zornitza Stark gene: MESD was added
gene: MESD was added to Mendeliome_VCGS. Sources: Other
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644
Review for gene: MESD was set to GREEN
Added comment: Five families reported.
Sources: Other
Mendeliome v0.738 EHHADH Zornitza Stark reviewed gene: EHHADH: Rating: RED; Mode of pathogenicity: None; Publications: 24401050; Phenotypes: Fanconi renotubular syndrome 3, OMIM#615605; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.736 VTN Zornitza Stark Mode of inheritance for gene: VTN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.734 VTN Zornitza Stark reviewed gene: VTN: Rating: RED; Mode of pathogenicity: None; Publications: 30377230; Phenotypes: Atypical haemolytic uraemic syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.734 ANLN Zornitza Stark Mode of inheritance for gene: ANLN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.732 ANLN Zornitza Stark reviewed gene: ANLN: Rating: AMBER; Mode of pathogenicity: None; Publications: 24676636, 30002222; Phenotypes: Focal segmental glomerulosclerosis 8, OMIM #616032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.730 ARHGAP24 Zornitza Stark Mode of inheritance for gene: ARHGAP24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.728 ARHGAP24 Zornitza Stark reviewed gene: ARHGAP24: Rating: RED; Mode of pathogenicity: None; Publications: 21911940; Phenotypes: FSGS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.726 CD2AP Zornitza Stark Mode of inheritance for gene: CD2AP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.724 CD2AP Zornitza Stark reviewed gene: CD2AP: Rating: AMBER; Mode of pathogenicity: None; Publications: 30612599, 17713465; Phenotypes: Glomerulosclerosis, focal segmental, 3, OMIM #607832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.723 ITSN1 Zornitza Stark gene: ITSN1 was added
gene: ITSN1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ITSN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITSN1 were set to 29773874
Review for gene: ITSN1 was set to GREEN
Added comment: 3 unrelated families with rare ITSN1 variants and SRNS/CNS or SSNS.
Sources: Expert list
Mendeliome v0.720 TNS2 Zornitza Stark gene: TNS2 was added
gene: TNS2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNS2 were set to 29773874
Phenotypes for gene: TNS2 were set to Nephrotic syndrome
Review for gene: TNS2 was set to GREEN
Added comment: Five families reported in this paper reporting multiple new SRNS genes.
Sources: Expert list
Mendeliome v0.717 DNASE2 Zornitza Stark gene: DNASE2 was added
gene: DNASE2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to 29259162; 31775019
Phenotypes for gene: DNASE2 were set to Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH
Review for gene: DNASE2 was set to GREEN
Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data.
Sources: Expert list
Mendeliome v0.715 IGHM Zornitza Stark gene: IGHM was added
gene: IGHM was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: IGHM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGHM were set to 12370281; 8890099
Phenotypes for gene: IGHM were set to Agammaglobulinemia 1, MIM# 601495
Review for gene: IGHM was set to GREEN
Added comment: Multiple families reported; please note a 40kb deletion as well as SNVs.
Sources: Expert list
Mendeliome v0.712 ANGPTL6 Zornitza Stark Mode of inheritance for gene: ANGPTL6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.710 ANGPTL6 Zornitza Stark reviewed gene: ANGPTL6: Rating: RED; Mode of pathogenicity: None; Publications: 29304371; Phenotypes: Cerebral aneurysm; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.709 NUP214 Sue White gene: NUP214 was added
gene: NUP214 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP214 were set to 31178128
Phenotypes for gene: NUP214 were set to epileptic encephalopathy; developmental regression; microcephaly
Penetrance for gene: NUP214 were set to Complete
Review for gene: NUP214 was set to GREEN
gene: NUP214 was marked as current diagnostic
Added comment: Sources: Literature
Mendeliome v0.707 ATP2B2 Sue White gene: ATP2B2 was added
gene: ATP2B2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP2B2 were set to progressive sensorineural deafness
Penetrance for gene: ATP2B2 were set to unknown
Review for gene: ATP2B2 was set to GREEN
gene: ATP2B2 was marked as current diagnostic
Added comment: Sources: Literature
Mendeliome v0.705 NPM1 Sue White gene: NPM1 was added
gene: NPM1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NPM1 were set to 31570891
Phenotypes for gene: NPM1 were set to radial ray defects; short stature; nail dsytrophy; bone marrow failure
Penetrance for gene: NPM1 were set to unknown
Review for gene: NPM1 was set to GREEN
Added comment: heterozygous variants cause dyskeratosis congenita
Sources: Literature
Mendeliome v0.703 AP2M1 Zornitza Stark gene: AP2M1 was added
gene: AP2M1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: AP2M1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AP2M1 were set to 31104773
Phenotypes for gene: AP2M1 were set to Intellectual developmental disorder 60 with seizures, MIM# 618587
Review for gene: AP2M1 was set to GREEN
Added comment: Four unrelated individuals reported, recurrent variant, NM_004068.3:c.508C>T or p.Arg170Trp.
Sources: Expert list
Mendeliome v0.699 ASXL3 Zornitza Stark Mode of inheritance for gene: ASXL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.698 ASXL3 Zornitza Stark reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28100473, 27901041, 23383720; Phenotypes: Bainbridge-Ropers syndrome (OMIM # 615485); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.697 RHOA Sue White gene: RHOA was added
gene: RHOA was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: RHOA was set to Other
Publications for gene: RHOA were set to 31570889
Phenotypes for gene: RHOA were set to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia
Penetrance for gene: RHOA were set to Complete
Review for gene: RHOA was set to GREEN
gene: RHOA was marked as current diagnostic
Added comment: mosaic heterozygous missense variants cause linear hypopigmentation, brain MRI changes with normal cognition, ocular and acral changes
Sources: Literature
Mendeliome v0.694 TNFRSF1A Zornitza Stark Mode of inheritance for gene: TNFRSF1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.693 TNFRSF1A Zornitza Stark reviewed gene: TNFRSF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10199409; Phenotypes: Periodic fever, familial, MIM# 142680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.686 DNMT3A Zornitza Stark Mode of inheritance for gene: DNMT3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.685 DNMT3A Zornitza Stark reviewed gene: DNMT3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30478443, 24614070; Phenotypes: Tatton-Brown-Rahman SYNDROME, OMIM# 615879, primordial dwarfism with intellectual disability and microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.684 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilm's tumour
Review for gene: TRIM28 was set to GREEN
Added comment: Eleven individuals with germline variants identified; plus one somatic. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development.
Sources: Literature
Mendeliome v0.682 YY1AP1 Zornitza Stark Mode of inheritance for gene: YY1AP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.681 YY1AP1 Zornitza Stark reviewed gene: YY1AP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Grange syndrome, MIM# 602531, stenosis/occlusion of multiple arteries; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.681 CBWD1 Zornitza Stark gene: CBWD1 was added
gene: CBWD1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CBWD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBWD1 were set to 31862704
Phenotypes for gene: CBWD1 were set to CAKUT
Review for gene: CBWD1 was set to RED
Added comment: A pair of siblings with homozygous deletion in this gene reported; functional data including animal model.
Sources: Literature
Mendeliome v0.679 DEF6 Zornitza Stark gene: DEF6 was added
gene: DEF6 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DEF6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEF6 were set to 31308374
Phenotypes for gene: DEF6 were set to Systemic autoimmunity
Review for gene: DEF6 was set to AMBER
Added comment: Three individuals from two families, some functional data.
Sources: Literature
Mendeliome v0.677 SETD5 Zornitza Stark Phenotypes for gene: SETD5 were changed from to Intellectual disability, autosomal dominant 23 (MIM # 615761)
Mendeliome v0.675 SETD5 Zornitza Stark Mode of inheritance for gene: SETD5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.673 ACTG2 Zornitza Stark Mode of inheritance for gene: ACTG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.672 ACTG2 Zornitza Stark reviewed gene: ACTG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Visceral myopathy, MIM#155310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.671 C19orf70 Zornitza Stark gene: C19orf70 was added
gene: C19orf70 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: C19orf70 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C19orf70 were set to 29618761; 27623147; 27485409
Phenotypes for gene: C19orf70 were set to Combined oxidative phosphorylation deficiency 37, MIM# 618329
Review for gene: C19orf70 was set to GREEN
Added comment: Three unrelated families reported. HGNC approved name MICOS13.
Sources: Expert list
Mendeliome v0.669 MIPEP Zornitza Stark gene: MIPEP was added
gene: MIPEP was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MIPEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIPEP were set to 27799064
Phenotypes for gene: MIPEP were set to Combined oxidative phosphorylation deficiency 31, MIM# 617228
Review for gene: MIPEP was set to GREEN
Added comment: Four unrelated children reported.
Sources: Expert list
Mendeliome v0.668 MRPS14 Zornitza Stark gene: MRPS14 was added
gene: MRPS14 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MRPS14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS14 were set to 30358850
Phenotypes for gene: MRPS14 were set to Combined oxidative phosphorylation deficiency 38, MIM# 618378
Review for gene: MRPS14 was set to RED
Added comment: Single individual reported, functional data.
Sources: Expert list
Mendeliome v0.667 PLEKHG2 Zornitza Stark gene: PLEKHG2 was added
gene: PLEKHG2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PLEKHG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHG2 were set to 26573021
Phenotypes for gene: PLEKHG2 were set to Leukodystrophy and acquired microcephaly with or without dystonia, MIM# 616763
Review for gene: PLEKHG2 was set to RED
Added comment: Five individuals from two unrelated families reported, same homozygous missense variant.
Sources: Expert list
Mendeliome v0.664 UFM1 Zornitza Stark Mode of inheritance for gene: UFM1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.663 UFM1 Zornitza Stark reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy, hypomyelinating, 14, MIM# 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.661 HIKESHI Zornitza Stark Mode of inheritance for gene: HIKESHI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.660 HIKESHI Zornitza Stark reviewed gene: HIKESHI: Rating: GREEN; Mode of pathogenicity: None; Publications: 26545878; Phenotypes: Leukodystrophy, hypomyelinating, 13, MIM# 616881; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.660 AIMP2 Zornitza Stark gene: AIMP2 was added
gene: AIMP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: AIMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AIMP2 were set to 29215095
Phenotypes for gene: AIMP2 were set to Leukodystrophy, hypomyelinating, 17 618006
Review for gene: AIMP2 was set to RED
Added comment: Two apparently unrelated consanguineous families, however same homozygous variant identified in both. Affected individuals had early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD). Brain imaging showed multiple abnormalities, including cerebral and cerebellar atrophy, thin corpus callosum, abnormal signals in the basal ganglia, and features suggesting hypo- or demyelination
Sources: Expert list
Mendeliome v0.658 TMEM63A Zornitza Stark gene: TMEM63A was added
gene: TMEM63A was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TMEM63A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63A were set to 31587869
Phenotypes for gene: TMEM63A were set to Leukodystrophy, hypomyelinating, 19, transient infantile, MIM# 618688
Review for gene: TMEM63A was set to GREEN
Added comment: Four unrelated families reported; in three individuals, the variant was de novo, and inherited from a deceased parent in the fourth.
Sources: Expert list
Mendeliome v0.655 EPRS Zornitza Stark Mode of inheritance for gene: EPRS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.654 EPRS Zornitza Stark reviewed gene: EPRS: Rating: GREEN; Mode of pathogenicity: None; Publications: 29576217; Phenotypes: Leukodystrophy, hypomyelinating, 15, MIM# 617951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.649 ROBO4 Zornitza Stark gene: ROBO4 was added
gene: ROBO4 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ROBO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROBO4 were set to 30455415
Phenotypes for gene: ROBO4 were set to bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Review for gene: ROBO4 was set to GREEN
Added comment: Two families, functional data, incomplete penetrance.
Sources: Literature
Mendeliome v0.647 MYMK Zornitza Stark gene: MYMK was added
gene: MYMK was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to 28681861
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome; OMIM #254940
Review for gene: MYMK was set to GREEN
Added comment: Sources: Expert list
Mendeliome v0.646 EDC3 Zornitza Stark gene: EDC3 was added
gene: EDC3 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: EDC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDC3 were set to 29685133; 25701870
Phenotypes for gene: EDC3 were set to Mental retardation, autosomal recessive 50, MIM# 616460
Review for gene: EDC3 was set to RED
Added comment: Single family reported; some functional data.
Sources: Expert list
Mendeliome v0.645 PUS3 Zornitza Stark reviewed gene: PUS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30308082, 28454995, 27055666, 30697592, 31444731; Phenotypes: Mental retardation, autosomal recessive 55, MIM# 617051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.644 EIF3F Zornitza Stark gene: EIF3F was added
gene: EIF3F was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to Mental retardation, autosomal recessive 67, MIM# 618295
Review for gene: EIF3F was set to GREEN
Added comment: Nine individuals from 7 families reported, all homozygous for the same missense variant, p.(Phe232Val). This variant is present at 0.12% frequency in non-Finnish Europeans in gnomad (no homozygotes).
Sources: Expert list
Mendeliome v0.643 RUSC2 Zornitza Stark Phenotypes for gene: RUSC2 were changed from to Mental retardation, autosomal recessive 61, MIM# 617773
Mendeliome v0.641 RUSC2 Zornitza Stark Mode of inheritance for gene: RUSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.639 RUSC2 Zornitza Stark reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27612186; Phenotypes: Mental retardation, autosomal recessive 61, MIM# 617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.638 RSRC1 Zornitza Stark gene: RSRC1 was added
gene: RSRC1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: RSRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSRC1 were set to 28640246; 29522154
Phenotypes for gene: RSRC1 were set to Intellectual developmental disorder, autosomal recessive 70, MIM# 618402
Review for gene: RSRC1 was set to AMBER
Added comment: Two unrelated families reported, 8 affected individuals.
Sources: Expert list
Mendeliome v0.636 METTL5 Zornitza Stark gene: METTL5 was added
gene: METTL5 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: METTL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METTL5 were set to 29302074; 31564433
Phenotypes for gene: METTL5 were set to Intellectual developmental disorder, autosomal recessive 72, MIM# 618665
Review for gene: METTL5 was set to GREEN
Added comment: Three unrelated families and animal model.
Sources: Expert list
Mendeliome v0.635 CXorf56 Zornitza Stark gene: CXorf56 was added
gene: CXorf56 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: CXorf56 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CXorf56 were set to 29374277
Phenotypes for gene: CXorf56 were set to Mental retardation, X-linked 107, MIM# 301013
Review for gene: CXorf56 was set to RED
Added comment: Single multigenerational family reported.
Sources: Expert list
Mendeliome v0.633 USP27X Zornitza Stark gene: USP27X was added
gene: USP27X was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: USP27X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: USP27X were set to 25644381
Phenotypes for gene: USP27X were set to Mental retardation, X-linked 105, MIM#300984
Review for gene: USP27X was set to AMBER
Added comment: Four individuals from two unrelated families reported.
Sources: Expert list
Mendeliome v0.631 KLHL15 Zornitza Stark gene: KLHL15 was added
gene: KLHL15 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KLHL15 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL15 were set to 25644381; 24817631
Phenotypes for gene: KLHL15 were set to Mental retardation, X-linked 103, MIM#300982
Review for gene: KLHL15 was set to AMBER
Added comment: Two families described: variants maternally inherited in both, one deletion, the other truncating.
Sources: Literature
Mendeliome v0.629 ODC1 Zornitza Stark gene: ODC1 was added
gene: ODC1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ODC1 were set to 30475435
Phenotypes for gene: ODC1 were set to Intellectual disability; macrocephaly; dysmorphism
Mode of pathogenicity for gene: ODC1 was set to Other
Review for gene: ODC1 was set to GREEN
Added comment: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature
Mendeliome v0.626 RPIA Zornitza Stark Mode of inheritance for gene: RPIA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.624 TRPM3 Zornitza Stark gene: TRPM3 was added
gene: TRPM3 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to 31278393
Phenotypes for gene: TRPM3 were set to Intellectual disability; epilepsy
Review for gene: TRPM3 was set to GREEN
Added comment: 8 unrelated individuals with de novo variants in this gene. Recurrent variant p.(Val837Met) identified in 7/8.
Sources: Literature
Mendeliome v0.621 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.619 UGP2 Zornitza Stark gene: UGP2 was added
gene: UGP2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Epileptic encephalopathy; intellectual disability; microcephaly
Review for gene: UGP2 was set to GREEN
Added comment: 22 individuals from 15 families reported with the same homozygous missense variant in this gene, chr2:64083454A > G, which causes a disruption of the start codon in the shorter isoform, which is expressed in brain.
Sources: Literature
Mendeliome v0.616 AGO3 Zornitza Stark Phenotypes for gene: AGO3 were changed from Intellectual disability; epilepsy; structural brain malformations to Intellectual disability
Mendeliome v0.615 AGO3 Zornitza Stark Phenotypes for gene: AGO3 were changed from to Intellectual disability; epilepsy; structural brain malformations
Mendeliome v0.613 AGO3 Zornitza Stark Mode of inheritance for gene: AGO3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.610 PIGP Zornitza Stark gene: PIGP was added
gene: PIGP was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PIGP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGP were set to 31139695
Phenotypes for gene: PIGP were set to Epileptic encephalopathy, early infantile, 55, MIM# 617599
Review for gene: PIGP was set to AMBER
Added comment: Three individuals from two unrelated families reported.
Sources: Expert list
Mendeliome v0.608 NEUROD2 Zornitza Stark gene: NEUROD2 was added
gene: NEUROD2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: NEUROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEUROD2 were set to 30323019
Phenotypes for gene: NEUROD2 were set to Epileptic encephalopathy, early infantile, 72, MIM# 618374
Review for gene: NEUROD2 was set to GREEN
Added comment: Two unrelated individuals with de novo missense variants in this gene, animal model.
Sources: Expert list
Mendeliome v0.606 GOT2 Zornitza Stark gene: GOT2 was added
gene: GOT2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GOT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOT2 were set to 31422819
Phenotypes for gene: GOT2 were set to Epileptic encephalopathy, early infantile, 82, MIM# 618721
Review for gene: GOT2 was set to GREEN
Added comment: Four individuals from three unrelated families reported. Treatment with pyridoxine and serine ameliorated the phenotype.
Sources: Expert list
Mendeliome v0.604 GLIS2 Zornitza Stark Mode of inheritance for gene: GLIS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.600 GLIS2 Zornitza Stark reviewed gene: GLIS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17618285, 23559409; Phenotypes: Nephronophthisis 7, OMIM#611498; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.598 IFT57 Zornitza Stark Mode of inheritance for gene: IFT57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.595 IFT74 Zornitza Stark gene: IFT74 was added
gene: IFT74 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT74 were set to 27486776
Phenotypes for gene: IFT74 were set to Bardet-Biedl syndrome 20, MIM# 617119
Review for gene: IFT74 was set to AMBER
Added comment: Single family and functional data.
Sources: Expert list
Mendeliome v0.592 IFT81 Zornitza Stark Mode of inheritance for gene: IFT81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.588 IFT81 Zornitza Stark reviewed gene: IFT81: Rating: AMBER; Mode of pathogenicity: None; Publications: 27666822; Phenotypes: Short-rib thoracic dysplasia 19 with or without polydactyly, MIM# 617895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.583 PDE6D Zornitza Stark Mode of inheritance for gene: PDE6D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.581 PDE6D Zornitza Stark reviewed gene: PDE6D: Rating: RED; Mode of pathogenicity: None; Publications: 24166846; Phenotypes: Joubert syndrome 22, OMIM #615665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.579 SLC41A1 Zornitza Stark Mode of inheritance for gene: SLC41A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.577 SLC41A1 Zornitza Stark reviewed gene: SLC41A1: Rating: RED; Mode of pathogenicity: None; Publications: 23661805; Phenotypes: Nephronophthisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.575 XPNPEP3 Zornitza Stark Mode of inheritance for gene: XPNPEP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.573 XPNPEP3 Zornitza Stark reviewed gene: XPNPEP3: Rating: RED; Mode of pathogenicity: None; Publications: 20179356; Phenotypes: Nephronophthisis-like nephropathy 1, OMIM #613159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.571 ZNF423 Zornitza Stark Mode of inheritance for gene: ZNF423 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.569 ZNF423 Zornitza Stark reviewed gene: ZNF423: Rating: RED; Mode of pathogenicity: None; Publications: 22863007; Phenotypes: Joubert syndrome 19, OMIM# 614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.568 PIGQ Zornitza Stark gene: PIGQ was added
gene: PIGQ was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PIGQ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGQ were set to 25558065; 24463883; 31148362
Phenotypes for gene: PIGQ were set to Epileptic encephalopathy, early infantile, 77, MIM# 618548
Review for gene: PIGQ was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Mendeliome v0.566 NTRK2 Zornitza Stark Mode of inheritance for gene: NTRK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.565 NTRK2 Zornitza Stark reviewed gene: NTRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083, 15494731, 27884935, 29100083; Phenotypes: Epileptic encephalopathy, early infantile, 58, MIM# 617830, Obesity, hyperphagia, and developmental delay, MIM# 613886; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.565 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert list
Mendeliome v0.563 PHACTR1 Zornitza Stark gene: PHACTR1 was added
gene: PHACTR1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PHACTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHACTR1 were set to 30256902
Phenotypes for gene: PHACTR1 were set to Epileptic encephalopathy, early infantile, 70, MIM# 618298
Review for gene: PHACTR1 was set to GREEN
Added comment: Three unrelated individuals reported with de novo variants in this gene.
Sources: Expert list
Mendeliome v0.561 GABRB1 Zornitza Stark gene: GABRB1 was added
gene: GABRB1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB1 were set to 23934111; 27273810; 31618474
Phenotypes for gene: GABRB1 were set to Epileptic encephalopathy, early infantile, 45, MIM# 617153
Review for gene: GABRB1 was set to GREEN
Added comment: Three individuals reported, two as part of large epilepsy cohorts.
Sources: Expert list
Mendeliome v0.558 GABRA2 Zornitza Stark Mode of inheritance for gene: GABRA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.557 GABRA2 Zornitza Stark reviewed gene: GABRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29422393; Phenotypes: Epileptic encephalopathy, early infantile, 78, MIM# 618557; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.557 GUF1 Zornitza Stark gene: GUF1 was added
gene: GUF1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GUF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUF1 were set to 26486472
Phenotypes for gene: GUF1 were set to Epileptic encephalopathy, early infantile, 40, MIM# 617065
Review for gene: GUF1 was set to RED
Added comment: Single family reported with homozygous missense in three sibs.
Sources: Expert list
Mendeliome v0.555 CPLX1 Zornitza Stark gene: CPLX1 was added
gene: CPLX1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: CPLX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPLX1 were set to 26539891; 28422131
Phenotypes for gene: CPLX1 were set to Epileptic encephalopathy, early infantile, 63, MIM# 617976
Review for gene: CPLX1 was set to GREEN
Added comment: Five individuals from three unrelated families reported in larger neurodevelopmental cohorts.
Sources: Expert list
Mendeliome v0.553 RNF13 Zornitza Stark gene: RNF13 was added
gene: RNF13 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: RNF13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF13 were set to 30595371
Phenotypes for gene: RNF13 were set to Epileptic encephalopathy, early infantile, 73, MIM# 618379
Mode of pathogenicity for gene: RNF13 was set to Other
Review for gene: RNF13 was set to GREEN
Added comment: Three unrelated individuals with de novo gain-of-function variants in this gene reported; severe neurodegenerative disorder, seizures are a prominent part of the phenotype.
Sources: Literature
Mendeliome v0.551 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30575854; 30970188
Phenotypes for gene: GLS were set to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Review for gene: GLS was set to GREEN
Added comment: Three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels (PMID: 30575854).

Another three unrelated individuals described with compound het variants, one of which is a triplet expansion in the 5' UTR (PMID: 30970188).
Sources: Expert list
Mendeliome v0.549 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 28007989; 25678555
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50, MIM# 616457
Review for gene: CAD was set to GREEN
Added comment: Five individuals from four unrelated families reported, seizures are a prominent part of the phenotype of this progressive neurometabolic condition.
Sources: Expert list
Mendeliome v0.546 PARS2 Zornitza Stark Mode of inheritance for gene: PARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.545 PARS2 Zornitza Stark reviewed gene: PARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29410512, 28077841, 25629079, 29915213; Phenotypes: Epileptic encephalopathy, early infantile, 75, MIM# 618437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.543 CHRNA3 Zornitza Stark Mode of inheritance for gene: CHRNA3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.542 CHRNA3 Zornitza Stark reviewed gene: CHRNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31708116; Phenotypes: CAKUT, dysautonomia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.541 NADSYN1 Zornitza Stark gene: NADSYN1 was added
gene: NADSYN1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral
Review for gene: NADSYN1 was set to GREEN
Added comment: Five individuals from four unrelated families.
Sources: Literature
Mendeliome v0.538 PPP1R12A Zornitza Stark Mode of inheritance for gene: PPP1R12A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.536 UQCRFS1 Zornitza Stark gene: UQCRFS1 was added
gene: UQCRFS1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCRFS1 were set to 31883641
Phenotypes for gene: UQCRFS1 were set to Mitochondrial Complex III deficiency; lactic acidosis; fetal bradycardia; hypertrophic cardiomyopathy; alopecia totalis
Review for gene: UQCRFS1 was set to GREEN
Added comment: Two unrelated families reported plus functional evidence.
Sources: Literature
Mendeliome v0.534 SPATC1L Zornitza Stark gene: SPATC1L was added
gene: SPATC1L was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: SPATC1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATC1L were set to 30177775
Phenotypes for gene: SPATC1L were set to Deafness
Review for gene: SPATC1L was set to AMBER
Added comment: Two families with compound het variants, and one family with heterozygous variant and dominant pattern of hearing loss described, some functional data.
Sources: Expert list
Mendeliome v0.532 WBP2 Zornitza Stark gene: WBP2 was added
gene: WBP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP2 were set to 26881968
Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM# 617639
Review for gene: WBP2 was set to AMBER
Added comment: Two unrelated families identified in a large cohort; supportive animal model data.
Sources: Expert list
Mendeliome v0.530 TMEM132E Zornitza Stark gene: TMEM132E was added
gene: TMEM132E was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM132E were set to 25331638
Phenotypes for gene: TMEM132E were set to Deafness, autosomal recessive 99, MIM# 618481
Review for gene: TMEM132E was set to AMBER
Added comment: Single family reported, supportive animal model.
Sources: Expert list
Mendeliome v0.529 GRAP Zornitza Stark gene: GRAP was added
gene: GRAP was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GRAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRAP were set to 30610177
Phenotypes for gene: GRAP were set to Deafness, autosomal recessive 114, MIM# 618456
Review for gene: GRAP was set to RED
Added comment: Two apparently unrelated Turkish families reported, however same homozygous missense variant, and SNP analysis indicated identity by descent.
Sources: Expert list
Mendeliome v0.527 SPNS2 Zornitza Stark gene: SPNS2 was added
gene: SPNS2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPNS2 were set to 25356849
Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM# 618457
Review for gene: SPNS2 was set to AMBER
Added comment: Single family reported, mouse model shows progressive hearing loss.
Sources: Expert list
Mendeliome v0.525 ESRP1 Zornitza Stark gene: ESRP1 was added
gene: ESRP1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESRP1 were set to 29107558
Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013
Review for gene: ESRP1 was set to AMBER
Added comment: Single family with affected sibs, mouse model.
Sources: Expert list
Mendeliome v0.524 SLC26A5 Zornitza Stark Phenotypes for gene: SLC26A5 were changed from to Deafness, autosomal recessive 61, MIM# 613865
Mendeliome v0.522 SLC26A5 Zornitza Stark Mode of inheritance for gene: SLC26A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.520 SLC26A5 Zornitza Stark reviewed gene: SLC26A5: Rating: RED; Mode of pathogenicity: None; Publications: 24164807; Phenotypes: Deafness, autosomal recessive 61, MIM# 613865; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.519 PPIP5K2 Zornitza Stark gene: PPIP5K2 was added
gene: PPIP5K2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIP5K2 were set to 29590114
Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM# 618422
Review for gene: PPIP5K2 was set to AMBER
Added comment: Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model.
Sources: Expert list
Mendeliome v0.517 ROR1 Zornitza Stark gene: ROR1 was added
gene: ROR1 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROR1 were set to 27162350
Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM# 617654
Review for gene: ROR1 was set to AMBER
Added comment: Single family, sibs with homozygous missense variant; mouse model.
Sources: Expert list
Mendeliome v0.515 RIPOR2 Zornitza Stark gene: RIPOR2 was added
gene: RIPOR2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: RIPOR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIPOR2 were set to 24958875
Phenotypes for gene: RIPOR2 were set to Deafness, autosomal recessive 104, MIM# 616515
Review for gene: RIPOR2 was set to AMBER
Added comment: Single family and animal model data.
Sources: Expert list
Mendeliome v0.514 PROC Zornitza Stark Phenotypes for gene: PROC were changed from to Thrombophilia due to protein C deficiency, autosomal dominant (176860); Thrombophilia due to protein C deficiency, autosomal recessive (612304)
Mendeliome v0.513 PROC Zornitza Stark Mode of inheritance for gene: PROC was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.512 PROC Chris Richmond reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: 22545135, 30925296; Phenotypes: Thrombophilia due to protein C deficiency, autosomal dominant (176860), Thrombophilia due to protein C deficiency, autosomal recessive (612304); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.511 CLDN9 Zornitza Stark gene: CLDN9 was added
gene: CLDN9 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN9 were set to 31175426; 19696885
Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive
Review for gene: CLDN9 was set to AMBER
Added comment: Single family with multiple sibs reported; mouse model exhibits deafness.
Sources: Literature
Mendeliome v0.509 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to 31198993
Phenotypes for gene: TOP2B were set to Autosomal dominant deafness
Review for gene: TOP2B was set to AMBER
Added comment: One multigenerational family where variant in this gene segregated; two additional variants identified in a cohort; supportive animal model data.
Sources: Literature
Mendeliome v0.507 AP1B1 Zornitza Stark gene: AP1B1 was added
gene: AP1B1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to 31630788; 31630791
Phenotypes for gene: AP1B1 were set to Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma
Review for gene: AP1B1 was set to GREEN
Added comment: Four unrelated families with bi-allelic LoF variants in this gene.
Sources: Literature
Mendeliome v0.505 ADCY1 Zornitza Stark Phenotypes for gene: ADCY1 were changed from to Deafness, autosomal recessive 44, MIM# 610154
Mendeliome v0.504 ADCY1 Zornitza Stark Mode of inheritance for gene: ADCY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.502 ADCY1 Zornitza Stark reviewed gene: ADCY1: Rating: RED; Mode of pathogenicity: None; Publications: 24482543; Phenotypes: Deafness, autosomal recessive 44, MIM# 610154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.502 BDP1 Zornitza Stark Mode of inheritance for gene: BDP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.501 BDP1 Zornitza Stark Phenotypes for gene: BDP1 were changed from to Deafness, autosomal recessive 112, MIM#618257
Mendeliome v0.498 BDP1 Zornitza Stark reviewed gene: BDP1: Rating: RED; Mode of pathogenicity: None; Publications: 24312468, 25060281; Phenotypes: Deafness, autosomal recessive 112, MIM#618257; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.498 CLIC5 Zornitza Stark Phenotypes for gene: CLIC5 were changed from to Deafness, autosomal recessive 103, MIM# 616042
Mendeliome v0.497 CLIC5 Zornitza Stark Mode of inheritance for gene: CLIC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.494 CLIC5 Zornitza Stark reviewed gene: CLIC5: Rating: AMBER; Mode of pathogenicity: None; Publications: 24781754, 17021174; Phenotypes: Deafness, autosomal recessive 103, MIM# 616042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.494 DIABLO Zornitza Stark Phenotypes for gene: DIABLO were changed from to Deafness, autosomal dominant 64, MIM# 614152
Mendeliome v0.492 DIABLO Zornitza Stark Mode of inheritance for gene: DIABLO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.490 DIABLO Zornitza Stark reviewed gene: DIABLO: Rating: RED; Mode of pathogenicity: None; Publications: 21722859, 10929711; Phenotypes: Deafness, autosomal dominant 64, MIM# 614152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.490 DIAPH3 Zornitza Stark Phenotypes for gene: DIAPH3 were changed from to Auditory neuropathy, autosomal dominant, 1, MIM#609129
Mendeliome v0.489 DIAPH3 Zornitza Stark Mode of inheritance for gene: DIAPH3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.486 DIAPH3 Zornitza Stark reviewed gene: DIAPH3: Rating: RED; Mode of pathogenicity: None; Publications: 23441200, 20624953; Phenotypes: Auditory neuropathy, autosomal dominant, 1, MIM#609129; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.485 DMXL2 Zornitza Stark gene: DMXL2 was added
gene: DMXL2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DMXL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMXL2 were set to 31688942; 30237576
Phenotypes for gene: DMXL2 were set to Epileptic encephalopathy, early infantile, 81, MIM# 618663
Review for gene: DMXL2 was set to GREEN
Added comment: Four unrelated families reported.
Sources: Literature
Mendeliome v0.484 ELMOD3 Zornitza Stark Phenotypes for gene: ELMOD3 were changed from to Deafness, autosomal recessive 88, MIM# 615429; Deafness, autosomal dominant
Mendeliome v0.482 ELMOD3 Zornitza Stark Mode of inheritance for gene: ELMOD3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.480 ELMOD3 Zornitza Stark reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 24039609, 31628468, 30284680, 29713870; Phenotypes: Deafness, autosomal recessive 88, MIM# 615429, Deafness, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.479 EPS8L2 Zornitza Stark gene: EPS8L2 was added
gene: EPS8L2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPS8L2 were set to 26282398; 23918390; 28281779
Phenotypes for gene: EPS8L2 were set to Deafness autosomal recessive 106, MIM# 617637
Review for gene: EPS8L2 was set to GREEN
Added comment: Two unrelated families and a mouse model.
Sources: Expert list
Mendeliome v0.478 GRXCR2 Zornitza Stark Phenotypes for gene: GRXCR2 were changed from to Deafness, autosomal recessive 101, MIM# 615837
Mendeliome v0.475 GRXCR2 Zornitza Stark reviewed gene: GRXCR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24619944; Phenotypes: Deafness, autosomal recessive 101, MIM# 615837; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.474 HARS Zornitza Stark Mode of inheritance for gene: HARS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.473 HARS Zornitza Stark reviewed gene: HARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 26072516; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2W, MIM# 616625; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.473 KITLG Zornitza Stark Mode of inheritance for gene: KITLG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.471 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Mendeliome v0.469 KITLG Zornitza Stark reviewed gene: KITLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 26522471; Phenotypes: Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.469 MIR96 Zornitza Stark Phenotypes for gene: MIR96 were changed from to Deafness, autosomal dominant 50, MIM# 613074
Mendeliome v0.467 MIR96 Zornitza Stark Mode of inheritance for gene: MIR96 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.465 MIR96 Zornitza Stark reviewed gene: MIR96: Rating: AMBER; Mode of pathogenicity: None; Publications: 19363479, 29325119; Phenotypes: Deafness, autosomal dominant 50, MIM# 613074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.463 NUP188 Zornitza Stark Mode of inheritance for gene: NUP188 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.461 NUP188 Zornitza Stark reviewed gene: NUP188: Rating: AMBER; Mode of pathogenicity: None; Publications: https://doi.org/10.1159/000504818, 28726809; Phenotypes: microcephaly, ID, cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.460 SLC5A6 Zornitza Stark gene: SLC5A6 was added
gene: SLC5A6 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 31754459; 27904971
Phenotypes for gene: SLC5A6 were set to Developmental delay; epilepsy; neurodegeneration
Review for gene: SLC5A6 was set to GREEN
Added comment: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature
Mendeliome v0.457 KIF23 Zornitza Stark Mode of inheritance for gene: KIF23 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.455 KIF23 Zornitza Stark reviewed gene: KIF23: Rating: RED; Mode of pathogenicity: None; Publications: 23570799; Phenotypes: Congenital dyserythropoietic anemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.453 ATP2B3 Zornitza Stark Mode of inheritance for gene: ATP2B3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.451 ATP2B3 Zornitza Stark reviewed gene: ATP2B3: Rating: AMBER; Mode of pathogenicity: None; Publications: 22912398, 27653636, 27632770; Phenotypes: Spinocerebellar ataxia, X-linked 1, MIM#302500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.450 CACNB4 Zornitza Stark Mode of inheritance for gene: CACNB4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.447 CACNB4 Zornitza Stark reviewed gene: CACNB4: Rating: AMBER; Mode of pathogenicity: None; Publications: 10762541, 9628818, 27003325; Phenotypes: Episodic ataxia, type 5, MIM#613855; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.447 CAPN1 Zornitza Stark Phenotypes for gene: CAPN1 were changed from to Spastic paraplegia 76, autosomal recessive, MIM#616907
Mendeliome v0.445 CAPN1 Zornitza Stark Mode of inheritance for gene: CAPN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.444 CAPN1 Zornitza Stark reviewed gene: CAPN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27153400; Phenotypes: Spastic paraplegia 76, autosomal recessive, MIM#616907; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.440 COA7 Zornitza Stark gene: COA7 was added
gene: COA7 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COA7 were set to 29718187; 27683825
Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387
Review for gene: COA7 was set to GREEN
Added comment: Five unrelated individuals reported with bi-allelic variants in this gene. Slowly progressive condition with variable onset, but at least three individuals presented at <5 years of age.
Sources: Expert list
Mendeliome v0.439 CCDC88C Zornitza Stark Mode of inheritance for gene: CCDC88C was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.436 CCDC88C Zornitza Stark Mode of inheritance for gene: CCDC88C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.434 CCDC88C Zornitza Stark reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 25062847, 30398676; Phenotypes: Spinocerebellar ataxia 40, MIM#616053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.433 COQ5 Zornitza Stark Mode of inheritance for gene: COQ5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.430 COQ5 Zornitza Stark reviewed gene: COQ5: Rating: RED; Mode of pathogenicity: None; Publications: 29044765; Phenotypes: Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.428 EEF2 Zornitza Stark Mode of inheritance for gene: EEF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.426 EEF2 Zornitza Stark reviewed gene: EEF2: Rating: RED; Mode of pathogenicity: None; Publications: 15732118, 23001565; Phenotypes: Spinocerebellar ataxia 26; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.425 FAT2 Zornitza Stark gene: FAT2 was added
gene: FAT2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: FAT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAT2 were set to 29053796
Phenotypes for gene: FAT2 were set to Spinocerebellar ataxia 45, MIM#617769
Review for gene: FAT2 was set to AMBER
Added comment: Segregates in one family, and identified in one apparently sporadic case. In vitro functional evidence.
Sources: Expert list
Mendeliome v0.423 GDAP2 Zornitza Stark gene: GDAP2 was added
gene: GDAP2 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: GDAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GDAP2 were set to 30084953
Phenotypes for gene: GDAP2 were set to Spinocerebellar ataxia, autosomal recessive 27, MIM#618369
Review for gene: GDAP2 was set to GREEN
Added comment: Two families and animal model.
Sources: Expert list
Mendeliome v0.419 MN1 Zornitza Stark Mode of inheritance for gene: MN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.418 MN1 Zornitza Stark reviewed gene: MN1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31834374, 31839203; Phenotypes: Intellectual disability, dysmophic features, rhombencephalosynapsis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.417 NDUFAF8 Zornitza Stark gene: NDUFAF8 was added
gene: NDUFAF8 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NDUFAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFAF8 were set to 31866046
Phenotypes for gene: NDUFAF8 were set to Leigh syndrome
Review for gene: NDUFAF8 was set to GREEN
Added comment: Three unrelated individuals with bi-allelic variants in this gene; functional data. Beware recurrent deep intronic splicing variant.
Sources: Literature
Mendeliome v0.415 EEF1B2 Zornitza Stark gene: EEF1B2 was added
gene: EEF1B2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1B2 were set to 31845318; 21937992
Phenotypes for gene: EEF1B2 were set to Intellectual disability
Review for gene: EEF1B2 was set to AMBER
Added comment: 5 individuals from two unrelated families described in the literature so far, no functional data but gene belongs to a family implicated in neurodevelopmental disorders.
Sources: Literature
Mendeliome v0.409 TBC1D8B Zornitza Stark Mode of inheritance for gene: TBC1D8B was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.408 TBC1D8B Zornitza Stark reviewed gene: TBC1D8B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30661770; Phenotypes: Nephrotic syndrome, type 20, MIM# 301028; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.408 ANKRD17 Zornitza Stark Mode of inheritance for gene: ANKRD17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.402 REV3L Zornitza Stark Mode of inheritance for gene: REV3L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.401 REV3L Belinda Chong reviewed gene: REV3L: Rating: GREEN; Mode of pathogenicity: None; Publications: 26068067, 26068067; Phenotypes: Moebius syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.399 FLG2 Zornitza Stark gene: FLG2 was added
gene: FLG2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: FLG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLG2 were set to 29758285; 28884927; 29505760
Phenotypes for gene: FLG2 were set to Peeling skin syndrome 6, MIM# 618084
Review for gene: FLG2 was set to GREEN
Added comment: 3 unrelated families reported.
Sources: Literature
Mendeliome v0.398 NLRP2 Zornitza Stark Phenotypes for gene: NLRP2 were changed from to female infertility; early embryonic arrest
Mendeliome v0.396 NLRP2 Zornitza Stark Mode of inheritance for gene: NLRP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.395 NLRP2 Belinda Chong reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30877238; Phenotypes: female infertility, early embryonic arrest; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.393 TBC1D32 Zornitza Stark Mode of inheritance for gene: TBC1D32 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.391 TBC1D32 Zornitza Stark reviewed gene: TBC1D32: Rating: RED; Mode of pathogenicity: None; Publications: 24285566; Phenotypes: Orofaciodigital syndrome type IX; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.391 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from to Dandy-Walker malformation; renal dysplasia; bone marrow failure
Mendeliome v0.389 EXOC3L2 Zornitza Stark Mode of inheritance for gene: EXOC3L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.388 NUP37 Zornitza Stark gene: NUP37 was added
gene: NUP37 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NUP37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP37 were set to 30179222
Phenotypes for gene: NUP37 were set to Nephrotic syndrome
Review for gene: NUP37 was set to RED
Added comment: Single family reported with nephrotic syndrome.
Sources: Literature
Mendeliome v0.386 NUP133 Zornitza Stark gene: NUP133 was added
gene: NUP133 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NUP133 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP133 were set to 30179222
Phenotypes for gene: NUP133 were set to Nephrotic syndrome, type 18, MIM#618177
Review for gene: NUP133 was set to GREEN
Added comment: Two unrelated families with functional data.
Sources: Literature
Mendeliome v0.385 NUP160 Zornitza Stark gene: NUP160 was added
gene: NUP160 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NUP160 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP160 were set to 30179222
Phenotypes for gene: NUP160 were set to Nephrotic syndrome, type 19, MIM#618178
Review for gene: NUP160 was set to RED
Added comment: Single family, no functional data.
Sources: Literature
Mendeliome v0.383 NUP85 Zornitza Stark gene: NUP85 was added
gene: NUP85 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NUP85 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP85 were set to 30179222
Phenotypes for gene: NUP85 were set to Nephrotic syndrome, type 17, MIM#618176
Review for gene: NUP85 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Literature
Mendeliome v0.380 XPO5 Zornitza Stark Mode of inheritance for gene: XPO5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.378 XPO5 Zornitza Stark reviewed gene: XPO5: Rating: AMBER; Mode of pathogenicity: None; Publications: 26878725; Phenotypes: Nephrotic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.376 NUP205 Zornitza Stark Mode of inheritance for gene: NUP205 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.374 NUP205 Zornitza Stark reviewed gene: NUP205: Rating: RED; Mode of pathogenicity: None; Publications: 26878725; Phenotypes: Nephrotic syndrome, type 13, MIM#616893; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.372 KANK4 Zornitza Stark gene: KANK4 was added
gene: KANK4 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: KANK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KANK4 were set to 25961457
Phenotypes for gene: KANK4 were set to Nephrotic syndrome
Review for gene: KANK4 was set to AMBER
Added comment: Two individuals from a single family reported; gene belongs to a family implicated in nephrotic syndrome.
Sources: Expert list
Mendeliome v0.370 KCNT2 Zornitza Stark gene: KCNT2 was added
gene: KCNT2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNT2 were set to 29069600; 29740868
Phenotypes for gene: KCNT2 were set to Epileptic encephalopathy, early infantile, 57, MIM#617771; Developmental and epileptic encephalopathy
Review for gene: KCNT2 was set to GREEN
Added comment: Reviewed by E Palmer: Ambrosino et al described 2 unrelated females with de novo variants in KCNT2. The first patient had the variant p.(Arg190His) had with West syndrome followed by Lennox-Gastaut syndrome , the second patient had the variant p.(Arg190Pro) and DEE with migrating focal seizures. Both variants were absent gnomad and had supportive in silico support for pathogenicity. In an electrophisological model both KCNT2 R190P and KCNT2 R190H increased maximal current density and shifted toward more negative membrane potential values the activation curve of KCNT2 channels, consistent with gain of function effects. PMID: 29740868.

Gururaj et al describe one male with de novo variant in KCNT2 p. (Phe240Leu) and early infantile epileptic encephalopathy. he variant was absent gnomad and supportive evidence of pathogenicity This variant was electrophysiologically modelled and revealed that the variant resulted in a 'change in function' demonstrating unusual altered selectivity in KNa channels.PMID: 29069600.
Sources: Literature
Mendeliome v0.368 PLS1 Zornitza Stark gene: PLS1 was added
gene: PLS1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PLS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLS1 were set to 31397523; 31432506; 30872814
Phenotypes for gene: PLS1 were set to Deafness
Review for gene: PLS1 was set to GREEN
Added comment: Non-syndromic deafness in 5 families with mono allelic variants in this gene. Mouse model.
Sources: Literature
Mendeliome v0.366 TASP1 Zornitza Stark gene: TASP1 was added
gene: TASP1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TASP1 were set to 31209944; 31350873
Phenotypes for gene: TASP1 were set to Developmental delay; microcephaly; dysmorphic features; congenital abnormalities
Review for gene: TASP1 was set to GREEN
Added comment: Four unrelated families reported; two with founder mutation. Protein interacts with KMT2A and KMT2D. Another infant with a de novo missense variant reported in a single infant with multiple congenital abnormalities, insufficient evidence for mono allelic disease at present.
Sources: Literature
Mendeliome v0.365 FST Zornitza Stark gene: FST was added
gene: FST was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: FST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FST were set to 31215115
Phenotypes for gene: FST were set to Cleft lip and palate
Review for gene: FST was set to RED
Added comment: Single family reported.
Sources: Literature
Mendeliome v0.363 GDF11 Zornitza Stark gene: GDF11 was added
gene: GDF11 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: GDF11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GDF11 were set to 31215115
Phenotypes for gene: GDF11 were set to Cleft lip and palate
Review for gene: GDF11 was set to AMBER
Added comment: Cleft lip and palate, and rib and vertebral hypersegmentation in a single family. Mouse model.
Sources: Literature
Mendeliome v0.361 PRDM13 Zornitza Stark gene: PRDM13 was added
gene: PRDM13 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PRDM13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM13 were set to 30710461
Phenotypes for gene: PRDM13 were set to Retinal dystrophy
Mode of pathogenicity for gene: PRDM13 was set to Other
Review for gene: PRDM13 was set to GREEN
Added comment: 8 individuals from three families reported with UPSTREAM NON-CODING variants in this gene.
Sources: Literature
Mendeliome v0.359 PPP1R12A Zornitza Stark reviewed gene: PPP1R12A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, holoprosencephaly, disorder of sex development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.357 ANKRD17 Zornitza Stark reviewed gene: ANKRD17: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, dysmorphic features; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.355 ZFHX3 Zornitza Stark Mode of inheritance for gene: ZFHX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.354 ZFHX3 Zornitza Stark reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.352 USP7 Zornitza Stark Mode of inheritance for gene: USP7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.351 USP7 Zornitza Stark reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30679821; Phenotypes: Intellectual disability, Autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.348 KLHL24 Tiong Tan Mode of inheritance for gene: KLHL24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.347 KLHL24 Tiong Tan reviewed gene: KLHL24: Rating: GREEN; Mode of pathogenicity: None; Publications: 29779254, 30120936; Phenotypes: Epidermolysis bullosa simplex, generalized, with scarring and hair loss OMIM#617294, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.346 SLC12A2 Zornitza Stark gene: SLC12A2 was added
gene: SLC12A2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SLC12A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A2 were set to 30740830
Phenotypes for gene: SLC12A2 were set to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation
Review for gene: SLC12A2 was set to AMBER
Added comment: Single individual with bi-alllelic deletion described; mouse model recapitulated the phenotype.
Sources: Literature
Mendeliome v0.344 PANK4 Zornitza Stark gene: PANK4 was added
gene: PANK4 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PANK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PANK4 were set to 30585370
Phenotypes for gene: PANK4 were set to Congenital posterior cataract
Review for gene: PANK4 was set to AMBER
Added comment: Variant segregated with cataract in single 4-generation family, functional data including mouse model.
Sources: Literature
Mendeliome v0.343 CSNK1E Zornitza Stark gene: CSNK1E was added
gene: CSNK1E was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CSNK1E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSNK1E were set to 30488659
Phenotypes for gene: CSNK1E were set to Epileptic encephalopathy
Review for gene: CSNK1E was set to RED
Added comment: De novo splicing variant reported but in conjunction with STXBP1 variants; authors postulate it may contribute to susceptibility. Also reports linking variants in this gene to psychiatric disorders.
Sources: Literature
Mendeliome v0.342 DST Zornitza Stark Phenotypes for gene: DST were changed from to Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653; Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425
Mendeliome v0.340 DST Zornitza Stark Mode of inheritance for gene: DST was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.339 DST Zornitza Stark reviewed gene: DST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522446, 30371979, 28468842; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VI, MIM#614653, Epidermolysis bullosa simplex, autosomal recessive 2, MIM#615425; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.338 DEGS1 Zornitza Stark gene: DEGS1 was added
gene: DEGS1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEGS1 were set to 30620338; 30620337
Phenotypes for gene: DEGS1 were set to Leukodystrophy, hypomyelinating, 18, MIM#618404
Review for gene: DEGS1 was set to GREEN
Added comment: 20 individuals from 14 unrelated families.
Sources: Literature
Mendeliome v0.337 POLD2 Zornitza Stark gene: POLD2 was added
gene: POLD2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: POLD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD2 were set to 31449058
Phenotypes for gene: POLD2 were set to Intellectual disability; immunodeficiency
Review for gene: POLD2 was set to RED
Added comment: Single family, functional data.
Sources: Literature
Mendeliome v0.335 ZNF292 Zornitza Stark gene: ZNF292 was added
gene: ZNF292 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ZNF292 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF292 were set to 31723249
Phenotypes for gene: ZNF292 were set to Intellectual disability; Autism; ADHD
Review for gene: ZNF292 was set to GREEN
Added comment: 28 families with spectrum of neurodevelopmental features (including ID, ASD, and ADHD) due to de novo ZNF292 variants (1 family inherited). No functional evidence of specific variants, but ZNF292 is highly expressed in the developing human brain.
Sources: Literature
Mendeliome v0.333 ZMIZ1 Zornitza Stark gene: ZMIZ1 was added
gene: ZMIZ1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMIZ1 were set to 30639322
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies; OMIM #618659
Review for gene: ZMIZ1 was set to GREEN
Added comment: 19 unrelated individuals with heterozygous variants in this gene reported.
Sources: Literature
Mendeliome v0.331 VAMP2 Zornitza Stark gene: VAMP2 was added
gene: VAMP2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: VAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAMP2 were set to 30929742
Phenotypes for gene: VAMP2 were set to Intellectual disability; Autism
Review for gene: VAMP2 was set to GREEN
Added comment: 5 unrelated patients with heterozygous de novo mutations in VAMP2, presenting with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms.
Sources: Literature
Mendeliome v0.328 TENM3 Zornitza Stark Mode of inheritance for gene: TENM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.327 TENM3 Zornitza Stark reviewed gene: TENM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30513139, 22766609, 27103084, 29753094; Phenotypes: Microphthalmia, syndromic 15, MIM#615145, coloboma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.326 TARS Zornitza Stark gene: TARS was added
gene: TARS was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS were set to 31374204
Phenotypes for gene: TARS were set to Trichothiodystrophy 7, nonphotosensitive; OMIM #618546
Review for gene: TARS was set to AMBER
Added comment: Clinical features of trichothiodystrophy (TTD) include ichthyosis, intellectual disability, decreased fertility, short stature.

2 unrelated patients with non-photosensitive-TTD, in whom limited clinical information was available (one with DD): one compound heterozygous TARS variants, second homozygous for TARS variant. They showed that the variants had a profound effect on TARS protein stability and enzymatic function.
Sources: Literature
Mendeliome v0.324 TANC2 Zornitza Stark gene: TANC2 was added
gene: TANC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TANC2 were set to 31616000
Phenotypes for gene: TANC2 were set to Intellectual disability; autism; epilepsy; dysmorphism
Review for gene: TANC2 was set to GREEN
Added comment: 19 families with potentially disruptive heterozygous TANC2 variants, including 16 likely gene-disrupting mutations and three intragenic microdeletions. Patients presented with autism, intellectual disability, delayed language and motor development, epilepsy, facial dysmorphism, with complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. No functional evidence of specific variants, but they show TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, and shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Sources: Literature
Mendeliome v0.322 SVBP Zornitza Stark gene: SVBP was added
gene: SVBP was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to 31363758; 30607023
Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569
Review for gene: SVBP was set to GREEN
Added comment: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature
Mendeliome v0.320 SOX4 Zornitza Stark gene: SOX4 was added
gene: SOX4 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SOX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX4 were set to 30661772
Phenotypes for gene: SOX4 were set to Coffin-Siris syndrome 10; OMIM #618506
Review for gene: SOX4 was set to GREEN
Added comment: 4 patients with syndromic DD/ID and de novo mutations in SOX4 gene. Functional assays demonstrated that the SOX4 proteins carrying these variants were unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells.
Sources: Literature
Mendeliome v0.317 SNRPE Zornitza Stark Mode of inheritance for gene: SNRPE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.316 SNRPE Zornitza Stark reviewed gene: SNRPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 31671093, 23246290; Phenotypes: Hypotrichosis 11, OMIM #615059; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.315 SCAPER Zornitza Stark gene: SCAPER was added
gene: SCAPER was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCAPER were set to 28794130; 31069901; 31192531; 30723319
Phenotypes for gene: SCAPER were set to Intellectual disability; retinitis pigmentosa
Review for gene: SCAPER was set to GREEN
Added comment: 28 patients from 14 unrelated families with ID and retinitis pigmentosa (some with BBS phenotype), and homozygous or compound heterozygous mutations in SCAPER gene.
Sources: Literature
Mendeliome v0.313 SCAMP5 Zornitza Stark gene: SCAMP5 was added
gene: SCAMP5 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCAMP5 were set to 31439720
Phenotypes for gene: SCAMP5 were set to Intellectual disability; seizures; autism
Mode of pathogenicity for gene: SCAMP5 was set to Other
Review for gene: SCAMP5 was set to GREEN
Added comment: 2 unrelated individuals with ASD, ID and seizures, with the same heterozygous de novo variant in SCAMP5 (p.Gly302Trp). Western blot analysis of proteins overexpressed in the Drosophila fat body showed strongly reduced levels of the SCAMP p.Gly302Trp protein compared with the wild-type protein, indicating that the mutant either reduced expression or increased turnover of the protein. The expression of the fly homologue of the human SCAMP5 p.Gly180Trp mutation caused similar eye and neuronal phenotypes as the expression of SCAMP RNAi, suggesting a dominant-negative effect.
Sources: Literature
Mendeliome v0.311 PPP2CA Zornitza Stark gene: PPP2CA was added
gene: PPP2CA was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PPP2CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2CA were set to 30595372
Phenotypes for gene: PPP2CA were set to Neurodevelopmental disorder and language delay with or without structural brain abnormalities; OMIM #618354
Review for gene: PPP2CA was set to GREEN
Added comment: 15 unrelated patients with a neurodevelopmental disorder with de novo heterozygous PPP2CA mutations, and 1 with partial deletion of PPP2CA. Functional studies showed complete PP2A dysfunction in 4 individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation.
Sources: Literature
Mendeliome v0.309 POU3F3 Zornitza Stark gene: POU3F3 was added
gene: POU3F3 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: POU3F3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU3F3 were set to 24550763; 31303265
Phenotypes for gene: POU3F3 were set to Intellectual disability
Review for gene: POU3F3 was set to GREEN
Added comment: 19 individuals with DD/ID/speech issues and heterozygous POU3F3 disruptions, most of which were de novo variants. Positive functional cell-based analyses of pathogenic variants.

1 patient reported with whole gene deletion and ID.
Sources: Literature
Mendeliome v0.308 PISD Zornitza Stark reviewed gene: PISD: Rating: GREEN; Mode of pathogenicity: None; Publications: 31263216, 30858161; Phenotypes: Intellectual disability, cataracts, retinal degeneration, microcephaly, deafness, short stature, white matter abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.308 PIGU Zornitza Stark reviewed gene: PIGU: Rating: GREEN; Mode of pathogenicity: None; Publications: 31353022; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 21, OMIM #618590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.307 PIGB Zornitza Stark gene: PIGB was added
gene: PIGB was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGB were set to 31256876
Phenotypes for gene: PIGB were set to Epileptic encephalopathy, early infantile, 80; OMIM #618580
Review for gene: PIGB was set to GREEN
Added comment: 10 unrelated families with biallelic mutations in PIGB, with global DD and/or ID, and seizures. Two had polymicrogyria, 4 had a peripheral neuropathy, and 2 had a clinical diagnosis of DOORS syndrome. Patient lymphocytes and fibroblasts showed variably decreased levels of cell surface GPI-anchored proteins, including CD16 and CD59. In vitro functional expression studies performed with some of the mutations in PIGB-null CHO cells showed that the mutant proteins were unable to fully restore expression of GPI-anchored surface proteins, consistent with a loss of function, although the mutations had variable effects.
Sources: Literature
Mendeliome v0.305 PIBF1 Zornitza Stark gene: PIBF1 was added
gene: PIBF1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33; OMIM #617767
Review for gene: PIBF1 was set to GREEN
Added comment: Three unrelated families plus three Hutterite families reported with bi-allelic variants in this gene.
Sources: Literature
Mendeliome v0.303 PHF21A Zornitza Stark gene: PHF21A was added
gene: PHF21A was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF21A were set to 31649809; 30487643; 22770980
Phenotypes for gene: PHF21A were set to Intellectual disability; dysmorphic features
Review for gene: PHF21A was set to GREEN
Added comment: 9 cases with intellectual disability and craniofacial anomalies (Potocki-Shaffer syndrome), with de novo truncating variants in PHF21A. No functional evidence of variants, but PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype.

2 other unrelated individuals with translocations disrupting PHF21A. Lymphoblastoid cell lines from translocation subjects showed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation.
Sources: Literature
Mendeliome v0.301 POLR2A Sue White gene: POLR2A was added
gene: POLR2A was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to 31353023
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM# 618603
Mode of pathogenicity for gene: POLR2A was set to Other
Review for gene: POLR2A was set to GREEN
Added comment: 11 unrelated individuals reported with de novo variants in this gene. Missense variants postulated to exert a dominant-negative effect; LoF variants by contrast resulted in milder phenotype.
Sources: Literature
Mendeliome v0.299 PAK1 Zornitza Stark gene: PAK1 was added
gene: PAK1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK1 were set to 31504246; 30290153
Phenotypes for gene: PAK1 were set to Intellectual developmental disorder with macrocephaly, seizures, and speech delay; OMIM #618158
Review for gene: PAK1 was set to GREEN
Added comment: 2 unrelated individuals with de novo PAK1 mutations, with developmental delay, secondary macrocephaly, seizures, and ataxic gait. Enhanced phosphorylation of the PAK1 targets JNK and AKT shown in fibroblasts of one subject and of c-JUN in those of both subjects compared with control subjects. In fibroblasts of the 2 affected individuals, they observed a trend toward enhanced PAK1 kinase activity. By using co-immunoprecipitation and size-exclusion chromatography, they observed a significantly reduced dimerization for both PAK1 mutants compared with wild-type PAK1.

4 unrelated individuals with intellectual disability, macrocephaly and seizures, with de novo heterozygous missense variants in PAK1.
Sources: Literature
Mendeliome v0.297 P4HTM Zornitza Stark gene: P4HTM was added
gene: P4HTM was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: P4HTM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HTM were set to 25078763; 30940925
Phenotypes for gene: P4HTM were set to Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities; OMIM #618493
Review for gene: P4HTM was set to GREEN
Added comment: 12 patients from 5 families with hypotonia, intellectual disability, and eye abnormalities, and homozygous or compound heterozygous pathogenic P4HTM gene variants. Segregated with the disorder in the families. In vitro functional expression studies of 3 of the P4HTM variants showed that they caused a significant decrease in the amount of soluble protein compared to wildtype.
Sources: Literature
Mendeliome v0.296 NLGN1 Zornitza Stark gene: NLGN1 was added
gene: NLGN1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NLGN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLGN1 were set to 30460678
Phenotypes for gene: NLGN1 were set to intellectual disability; autism
Review for gene: NLGN1 was set to RED
Added comment: homozygous variant in the NLGN1 gene found in a pair of monozygotic twin brothers with intellectual disability and autism. Segregated with disease. No functional studies.
Sources: Literature
Mendeliome v0.294 NFASC Zornitza Stark gene: NFASC was added
gene: NFASC was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to 31501903; 28940097; 30124836; 30850329; 31608123
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction; OMIM #618356
Review for gene: NFASC was set to GREEN
Added comment: > 10 unrelated families reported, exhibiting a neurodevelopmental disorder (intellectual disability, developmental delay, motor impairment, speech difficulties, early onset demyelinating neuropathy), with homozygous variants in NFASC. Segregated with the disorder in the family. Some studies with functional evidence.
Sources: Literature
Mendeliome v0.293 NCAPD2 Zornitza Stark Phenotypes for gene: NCAPD2 were changed from to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Mendeliome v0.291 NCAPD2 Zornitza Stark Mode of inheritance for gene: NCAPD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.290 NCAPD2 Zornitza Stark reviewed gene: NCAPD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31056748, 27737959, 28097321; Phenotypes: Microcephaly 21, primary, autosomal recessive, OMIM #617983; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.290 MEPCE Zornitza Stark gene: MEPCE was added
gene: MEPCE was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MEPCE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPCE were set to 31467394
Phenotypes for gene: MEPCE were set to Intellectual disability; seizures
Review for gene: MEPCE was set to RED
Added comment: 1 patient with global DD and seizures with de novo MEPCE nonsense variant. mRNA and protein analyses identified nonsense-mediated mRNA decay to underlie the decreased amount of MEPCE in patient fibroblasts followed by LARP7 and 7SK snRNA downregulation and HEXIM1 upregulation. Flavopiridol treatment and ectopic MEPCE protein expression in patient fibroblasts rescued increased expression of six RNAP II-sensitive genes and suggested a possible repressive effect of MEPCE on P-TEFb-dependent transcription of specific genes.
Sources: Literature
Mendeliome v0.288 MAST1 Zornitza Stark gene: MAST1 was added
gene: MAST1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 31721002; 30449657
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; OMIM #618273
Review for gene: MAST1 was set to GREEN
Added comment: 6 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene. In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls.

1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1.
Sources: Literature
Mendeliome v0.287 MACROD2 Zornitza Stark gene: MACROD2 was added
gene: MACROD2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: MACROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACROD2 were set to 31055587
Phenotypes for gene: MACROD2 were set to intellectual disability; dysmorphic features; microcephaly
Review for gene: MACROD2 was set to RED
Added comment: 1 family with a few affected with microcephaly, ID, dysmorphic features, and polydactyly. Deletion of chromosome 20p12.1 involving the MACROD2 gene was found in several members of the family. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion.
Sources: Literature
Mendeliome v0.285 LSS Zornitza Stark gene: LSS was added
gene: LSS was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to 30723320
Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275; Intellectual disability
Review for gene: LSS was set to GREEN
Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance.
Sources: Literature
Mendeliome v0.284 LSM1 Zornitza Stark gene: LSM1 was added
gene: LSM1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: LSM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM1 were set to 31010896
Phenotypes for gene: LSM1 were set to intellectual disability; congenital abnormalities
Review for gene: LSM1 was set to RED
Added comment: 1 family with 2 siblings with global DD, multiple congenital anomalies, and abnormal eye movements, with homozygous splice variant in LSM1. Segregated with the phenotype in the family. Expression studies revealed absence of expression of the canonical isoform in the affected individuals. The Lsm1 knockout mice have a partially overlapping phenotype that affects the brain, heart, and eye.
Sources: Literature
Mendeliome v0.282 LMAN2L Zornitza Stark gene: LMAN2L was added
gene: LMAN2L was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: LMAN2L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LMAN2L were set to 31020005; 26566883
Phenotypes for gene: LMAN2L were set to Mental retardation, autosomal recessive, 52; OMIM #616887
Review for gene: LMAN2L was set to AMBER
Added comment: 1 consanguineous family with 7 individuals with ID and epilepsy, with homozygous LMAN2L missense mutation. Segregated with disease in family, and unaffected family members were heterozygous variant carriers. No functional studies.

1 non-consanguineous family with 4 affected with heterozygous frameshift LMAN2L mutation. Segregates in family. Mutation eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane.
Sources: Literature
Mendeliome v0.281 KDM3B Zornitza Stark gene: KDM3B was added
gene: KDM3B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to 30929739
Phenotypes for gene: KDM3B were set to Intellectual disability; dysmorphic features; short stature
Review for gene: KDM3B was set to GREEN
Added comment: 14 unrelated individuals and 3 affected parents with varying degrees of ID, DD, short stature, dysmorphism, and de novo or inherited pathogenic variants in KDM3B. No functional studies.
Sources: Literature
Mendeliome v0.279 GRIA2 Zornitza Stark gene: GRIA2 was added
gene: GRIA2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: GRIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIA2 were set to 31300657
Phenotypes for gene: GRIA2 were set to Intellectual disability; autism; Rett-like features; epileptic encephalopathy
Review for gene: GRIA2 was set to GREEN
Added comment: 28 unrelated patients with ID, ASD, Rett-like features, seizures/EE, and de novo heterozygous GRIA2 mutations. In functional expression studies, mutations led to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification.
Sources: Literature
Mendeliome v0.276 ADGRG6 Zornitza Stark Mode of inheritance for gene: ADGRG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.273 GABRA5 Zornitza Stark gene: GABRA5 was added
gene: GABRA5 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: GABRA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA5 were set to 31056671; 29961870
Phenotypes for gene: GABRA5 were set to Epileptic encephalopathy, early infantile, 79; OMIM #618559
Review for gene: GABRA5 was set to GREEN
Added comment: 3 unrelated patients with de novo heterozygous missense mutations in GABRA5 gene. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current.
Sources: Literature
Mendeliome v0.271 FRY Zornitza Stark gene: FRY was added
gene: FRY was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRY were set to 31487712; 27457812; 21937992
Phenotypes for gene: FRY were set to Intellectual disability
Review for gene: FRY was set to AMBER
Added comment: 1 patient with ID/DD and a novel homozygous deletion involving FRY gene identified by genomic SNP microarray. No functional evidence.

2 consanguineous families with 6 affected individuals with ID, and homozygous mutations of FRY. No functional evidence.
Sources: Literature
Mendeliome v0.269 FBXL3 Zornitza Stark gene: FBXL3 was added
gene: FBXL3 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: FBXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL3 were set to 30481285
Phenotypes for gene: FBXL3 were set to Intellectual developmental disorder with short stature, facial anomalies, and speech defects; OMIM #606220
Review for gene: FBXL3 was set to GREEN
Added comment: Three unrelated families, multiple affected individuals.
Sources: Literature
Mendeliome v0.268 ETS1 Zornitza Stark gene: ETS1 was added
gene: ETS1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ETS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ETS1 were set to 31160359
Phenotypes for gene: ETS1 were set to Intellectual disability
Review for gene: ETS1 was set to RED
Added comment: Single individual with de novo truncating variant in this gene; gene is Jacobsen syndrome critical region.
Sources: Literature
Mendeliome v0.267 ELMOD1 Zornitza Stark gene: ELMOD1 was added
gene: ELMOD1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ELMOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELMOD1 were set to 31327155
Phenotypes for gene: ELMOD1 were set to Intellectual disability
Review for gene: ELMOD1 was set to RED
Added comment: Single family reported.
Sources: Literature
Mendeliome v0.265 EEF1D Zornitza Stark gene: EEF1D was added
gene: EEF1D was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1D were set to 30787422; 28097321
Phenotypes for gene: EEF1D were set to Intellectual disability
Review for gene: EEF1D was set to AMBER
Added comment: Two unrelated families reported; one as part of a very large cohort of consanguineous families reporting multiple new candidate genes. No functional data.
Sources: Literature
Mendeliome v0.263 DYNC1I2 Zornitza Stark gene: DYNC1I2 was added
gene: DYNC1I2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Review for gene: DYNC1I2 was set to GREEN
Added comment: Five individuals from three unrelated families reported.
Sources: Literature
Mendeliome v0.262 DTYMK Zornitza Stark gene: DTYMK was added
gene: DTYMK was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DTYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DTYMK were set to 31271740
Phenotypes for gene: DTYMK were set to Intellectual disability; microcephaly
Review for gene: DTYMK was set to RED
Added comment: Single family, two affected sibs with compound het variants reported.
Sources: Literature
Mendeliome v0.261 DNAJA1 Zornitza Stark gene: DNAJA1 was added
gene: DNAJA1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DNAJA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJA1 were set to 30972502
Phenotypes for gene: DNAJA1 were set to Intellectual disability; seizures
Review for gene: DNAJA1 was set to RED
Added comment: Single family with multiple affected individuals reported with bi-allelic truncating variant in this gene.
Sources: Literature
Mendeliome v0.260 DLL1 Zornitza Stark Phenotypes for gene: DLL1 were changed from to Intellectual disability; autism; seizures; variable brain abnormalities; scoliosis
Mendeliome v0.258 DLL1 Zornitza Stark Mode of inheritance for gene: DLL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.257 DLL1 Zornitza Stark reviewed gene: DLL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31353024; Phenotypes: Intellectual disability, autism, seizures, variable brain abnormalities, scoliosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.256 DDX6 Zornitza Stark gene: DDX6 was added
gene: DDX6 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: DDX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX6 were set to 31422817
Phenotypes for gene: DDX6 were set to Intellectual developmental disorder with impaired language and dysmorphic facies, MIM#618653
Review for gene: DDX6 was set to GREEN
Added comment: Five unrelated individuals reported with 5 different de novo heterozygous missense mutations in exon 11 of the DDX6 gene. All variants occurred at conserved residues in either the QxxR or V motifs within the second RecA-2 domain of the helicase core; this region is involved in RNA and/or ATP binding, suggesting functional consequences.
Sources: Literature
Mendeliome v0.253 CYFIP2 Zornitza Stark Mode of inheritance for gene: CYFIP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.252 CYFIP2 Zornitza Stark reviewed gene: CYFIP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29534297; Phenotypes: Epileptic encephalopathy, early infantile, 65, MIM#618008; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.251 CSDE1 Zornitza Stark gene: CSDE1 was added
gene: CSDE1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CSDE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSDE1 were set to 31579823
Phenotypes for gene: CSDE1 were set to Autism; intellectual disability; seizures; macrocephaly
Review for gene: CSDE1 was set to GREEN
Added comment: 18 families reported with high impact (stoppage/frameshift) variants in this gene. Eight de novo, eight inherited, two with undetermined inheritance. Functional data. Parents who had the variants were also affected, though generally more mildly.
Sources: Literature
Mendeliome v0.250 CNTN6 Zornitza Stark gene: CNTN6 was added
gene: CNTN6 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CNTN6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNTN6 were set to 30836150; 28641109; 29983269
Phenotypes for gene: CNTN6 were set to Intellectual disability; autism; Tourette syndrome; schizophrenia
Review for gene: CNTN6 was set to RED
Added comment: Conflicting evidence based on CNV data, no SNVs identified.
Sources: Literature
Mendeliome v0.249 CMAS Zornitza Stark gene: CMAS was added
gene: CMAS was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CMAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CMAS were set to 31495922
Phenotypes for gene: CMAS were set to Intellectual disability
Review for gene: CMAS was set to RED
Added comment: Single family, no functional data.
Sources: Literature
Mendeliome v0.247 CDK8 Zornitza Stark gene: CDK8 was added
gene: CDK8 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK8 were set to 30905399
Phenotypes for gene: CDK8 were set to Intellectual disability; dysmorphism; congenital abnormalities; seizures
Review for gene: CDK8 was set to GREEN
Added comment: 12 unrelated individuals, missense variants demonstrated as de novo in 10. All variants localize to the ATP-binding pocket of the kinase domain.
Sources: Literature
Mendeliome v0.244 RNF113A Zornitza Stark Mode of inheritance for gene: RNF113A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.242 RNF113A Zornitza Stark reviewed gene: RNF113A: Rating: AMBER; Mode of pathogenicity: None; Publications: 25612912, 31793730; Phenotypes: Trichothiodystrophy 5, nonphotosensitive, OMIM #300953; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.241 PUS7 Zornitza Stark gene: PUS7 was added
gene: PUS7 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342
Review for gene: PUS7 was set to GREEN
Added comment: 11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.
Sources: Literature
Mendeliome v0.239 SEMA5A Zornitza Stark gene: SEMA5A was added
gene: SEMA5A was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SEMA5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA5A were set to 26395558
Phenotypes for gene: SEMA5A were set to Intellectual disability; autism
Review for gene: SEMA5A was set to AMBER
Added comment: 1 patient with de novo translocation t(5;22)(p15.3;q11.21) and ASD and ID. At the translocation breakpoint on chromosome 5, they observed a 861-kb deletion encompassing the end of the SEMA5A gene. No functional studies.

2 patients with ASD and predicted deleterious heterozygous variants (maternally inherited). No functional studies
Sources: Literature
Mendeliome v0.237 SMARCC2 Zornitza Stark gene: SMARCC2 was added
gene: SMARCC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SMARCC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC2 were set to 30580808
Phenotypes for gene: SMARCC2 were set to Coffin-Siris syndrome 8; OMIM #618362
Review for gene: SMARCC2 was set to GREEN
Added comment: 15 individuals with variable degrees of neurodevelopmental delay, growth retardation, prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features.
Sources: Literature
Mendeliome v0.235 SMARCD1 Zornitza Stark gene: SMARCD1 was added
gene: SMARCD1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SMARCD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCD1 were set to 30879640
Phenotypes for gene: SMARCD1 were set to Intellectual disability; dysmorphic features
Review for gene: SMARCD1 was set to GREEN
Added comment: 5 individuals with heterozygous SMARCD1 variants (4 de novo, 1 unk), and developmental delay, intellectual disability, hypotonia, feeding difficulties, dysmorphisms, and small hands and feet.
Sources: Literature
Mendeliome v0.233 BRSK2 Zornitza Stark gene: BRSK2 was added
gene: BRSK2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: BRSK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK2 were set to 30879638
Phenotypes for gene: BRSK2 were set to Intellectual disability; autism
Review for gene: BRSK2 was set to GREEN
Added comment: Nine unrelated individuals with heterozygous variants in this gene; six confirmed de novo (parents available).
Sources: Literature
Mendeliome v0.231 BCORL1 Zornitza Stark gene: BCORL1 was added
gene: BCORL1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: BCORL1 were set to 24123876; 30941876
Phenotypes for gene: BCORL1 were set to Shukla-Vernon syndrome, MIM#301029
Review for gene: BCORL1 was set to GREEN
Added comment: Four unrelated families reported altogether; some mothers mildly affected.
Sources: Literature
Mendeliome v0.229 BCL11B Zornitza Stark gene: BCL11B was added
gene: BCL11B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: BCL11B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BCL11B were set to 29985992
Phenotypes for gene: BCL11B were set to Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, MIM# 618092
Review for gene: BCL11B was set to GREEN
Added comment: Nine unrelated individuals, all but one with de novo variants in this gene and syndromic ID/immunodeficiency. Most variants located in the last exon (exon 4) and are predicted to escape nonsense-mediated mRNA decay.
Sources: Literature
Mendeliome v0.228 ATN1 Zornitza Stark Phenotypes for gene: ATN1 were changed from to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, MIM#618494
Mendeliome v0.226 ATN1 Zornitza Stark Mode of inheritance for gene: ATN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.225 ATN1 Zornitza Stark reviewed gene: ATN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30827498; Phenotypes: Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, MIM#618494; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.224 APC2 Zornitza Stark gene: APC2 was added
gene: APC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677
Review for gene: APC2 was set to GREEN
Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Sources: Literature
Mendeliome v0.222 ALKBH8 Zornitza Stark gene: ALKBH8 was added
gene: ALKBH8 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ALKBH8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALKBH8 were set to 31079898
Phenotypes for gene: ALKBH8 were set to Intellectual developmental disorder, autosomal recessive 71, MIM#618504
Review for gene: ALKBH8 was set to GREEN
Added comment: Two families and functional data.
Sources: Literature
Mendeliome v0.220 ACTL6B Zornitza Stark gene: ACTL6B was added
gene: ACTL6B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: ACTL6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACTL6B were set to 31134736; 31031012; 30656450; 30237576
Phenotypes for gene: ACTL6B were set to Epileptic encephalopathy, early infantile, 76, MIM# 618468; Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470
Review for gene: ACTL6B was set to GREEN
Added comment: Over 10 unrelated individuals reported in the literature.
Sources: Literature
Mendeliome v0.219 SELENOI Zornitza Stark Phenotypes for gene: SELENOI were changed from to developmental delay; spasticity; periventricular white mater abnormalities; peripheral neuropathy; seizures; bifid uvula in some affected individuals; microcephaly
Mendeliome v0.218 SELENOI Zornitza Stark Mode of inheritance for gene: SELENOI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.216 SELENOI Zornitza Stark reviewed gene: SELENOI: Rating: AMBER; Mode of pathogenicity: None; Publications: 28052917; Phenotypes: developmental delay, spasticity, periventricular white mater abnormalities, peripheral neuropathy, seizures, bifid uvula in some affected individuals, microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.215 PPP1R21 Zornitza Stark gene: PPP1R21 was added
gene: PPP1R21 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: PPP1R21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R21 were set to 30520571
Phenotypes for gene: PPP1R21 were set to Hypotonia; intellectual disability; white matter abnormalities
Review for gene: PPP1R21 was set to GREEN
Added comment: At least four unrelated families reported.
Sources: Literature
Mendeliome v0.213 PHC1 Zornitza Stark Phenotypes for gene: PHC1 were changed from to Microcephaly 11, primary, autosomal recessive, MIM#615414
Mendeliome v0.212 PHC1 Zornitza Stark Mode of inheritance for gene: PHC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.210 PHC1 Zornitza Stark reviewed gene: PHC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23418308; Phenotypes: Microcephaly 11, primary, autosomal recessive, MIM#615414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.210 TBX4 Zornitza Stark Phenotypes for gene: TBX4 were changed from to Posterior amelia with pelvis and pulmonary hypoplasia; small patella syndrome
Mendeliome v0.208 TBX4 Zornitza Stark Mode of inheritance for gene: TBX4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.207 TBX4 Zornitza Stark reviewed gene: TBX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31761294; Phenotypes: Posterior amelia with pelvis and pulmonary hypoplasia, small patella syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.206 OXR1 Zornitza Stark gene: OXR1 was added
gene: OXR1 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to 31785787
Phenotypes for gene: OXR1 were set to Intellectual disability; seizures; cerebellar atrophy
Review for gene: OXR1 was set to GREEN
Added comment: Five individuals from three families.
Sources: Literature
Mendeliome v0.205 TMX2 Zornitza Stark Phenotypes for gene: TMX2 were changed from to Microcephaly; ID; brain malformations
Mendeliome v0.203 TMX2 Zornitza Stark Mode of inheritance for gene: TMX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.202 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31735293, 31586943; Phenotypes: Microcephaly, ID, brain malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.202 NOP10 Zornitza Stark Phenotypes for gene: NOP10 were changed from to Dyskeratosis congenita, autosomal recessive 1, MIM#224230
Mendeliome v0.200 NOP10 Zornitza Stark Mode of inheritance for gene: NOP10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.195 NIN Zornitza Stark Mode of inheritance for gene: NIN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.193 NIN Zornitza Stark reviewed gene: NIN: Rating: RED; Mode of pathogenicity: None; Publications: 22933543; Phenotypes: Seckel syndrome 7, MIM#614851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.191 NECAP1 Zornitza Stark Mode of inheritance for gene: NECAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.188 EXT2 Zornitza Stark Mode of inheritance for gene: EXT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.184 NDUFB9 Zornitza Stark Mode of inheritance for gene: NDUFB9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.182 NDUFB9 Zornitza Stark reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 22200994; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.180 MRPS16 Zornitza Stark Mode of inheritance for gene: MRPS16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.175 MRPL3 Zornitza Stark Mode of inheritance for gene: MRPL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.169 CDK16 Zornitza Stark gene: CDK16 was added
gene: CDK16 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: CDK16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CDK16 were set to 25644381
Phenotypes for gene: CDK16 were set to Intellectual disability
Review for gene: CDK16 was set to AMBER
Added comment: Single family described in this manuscript describing multiple candidate genes for XLID.
Sources: Expert list
Mendeliome v0.167 MIR17HG Zornitza Stark gene: MIR17HG was added
gene: MIR17HG was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: MIR17HG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MIR17HG were set to 25391829; 21892160
Phenotypes for gene: MIR17HG were set to Feingold syndrome 2; OMIM #614326
Review for gene: MIR17HG was set to GREEN
Added comment: 4 unrelated cases reported - 3 with gene deletions, 1 with SNV
Sources: Expert list
Mendeliome v0.165 KLF7 Zornitza Stark gene: KLF7 was added
gene: KLF7 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KLF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLF7 were set to 29251763
Phenotypes for gene: KLF7 were set to Intellectual disability
Review for gene: KLF7 was set to GREEN
Added comment: Four unrelated individuals with de novo missense variants; animal model data supportive.
Sources: Literature
Mendeliome v0.162 KANK1 Zornitza Stark Mode of inheritance for gene: KANK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.160 KANK1 Zornitza Stark reviewed gene: KANK1: Rating: RED; Mode of pathogenicity: None; Publications: 25961457, 29729439, 30684669, 16301218; Phenotypes: Nephrotic syndrome, Cerebral palsy, spastic quadriplegic, 2, MIM#612900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.158 IGF2 Zornitza Stark Mode of inheritance for gene: IGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.157 IGF2 Zornitza Stark reviewed gene: IGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31544945, 26154720; Phenotypes: Growth restriction, severe, with distinctive facies, MIM#616489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.155 GORAB Zornitza Stark Mode of inheritance for gene: GORAB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.154 GORAB Zornitza Stark reviewed gene: GORAB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Geroderma osteodysplasticum, MIM#231070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.152 GAD1 Zornitza Stark Mode of inheritance for gene: GAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.148 FRMPD4 Zornitza Stark gene: FRMPD4 was added
gene: FRMPD4 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: FRMPD4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FRMPD4 were set to 25644381; 29267967
Phenotypes for gene: FRMPD4 were set to Mental retardation, X-linked 104, MIM#300983
Review for gene: FRMPD4 was set to GREEN
Added comment: Multiple affected individuals from unrelated families reported.
Sources: Expert list
Mendeliome v0.147 FBXO31 Zornitza Stark gene: FBXO31 was added
gene: FBXO31 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: FBXO31 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXO31 were set to 24623383
Phenotypes for gene: FBXO31 were set to Mental retardation, autosomal recessive 45, MIM#615979
Review for gene: FBXO31 was set to RED
Added comment: Single consanguineous family reported with homozygous truncating variant, limited functional evidence.
Sources: Expert list
Mendeliome v0.145 CFAP57 Sebastian Lunke reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: bioRxiv 773028, doi: https://doi.org/10.1101/773028; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.143 EXOSC2 Zornitza Stark Mode of inheritance for gene: EXOSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.138 ERMARD Zornitza Stark Mode of inheritance for gene: ERMARD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.136 ERMARD Zornitza Stark reviewed gene: ERMARD: Rating: RED; Mode of pathogenicity: None; Publications: 24056535, 27087860; Phenotypes: Periventricular nodular heterotopia 6, MIM#615544; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.134 EOMES Zornitza Stark Mode of inheritance for gene: EOMES was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.130 DPYS Zornitza Stark Mode of inheritance for gene: DPYS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.129 DPYS Zornitza Stark reviewed gene: DPYS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dihydropyrimidinuria, MIM#222748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.128 DNAJC12 Zornitza Stark Mode of inheritance for gene: DNAJC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.124 DDB1 Zornitza Stark Mode of inheritance for gene: DDB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.123 DDB1 Zornitza Stark reviewed gene: DDB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.123 CTNNA2 Zornitza Stark Phenotypes for gene: CTNNA2 were changed from to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Mendeliome v0.121 CTNNA2 Zornitza Stark Mode of inheritance for gene: CTNNA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.119 CPA6 Zornitza Stark reviewed gene: CPA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25875328, 21922598, 23105115; Phenotypes: Epilepsy, familial temporal lobe, 5, MIM#614417, Febrile seizures, familial, 11, MIM#614418; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.118 CP Zornitza Stark Mode of inheritance for gene: CP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.117 CP Zornitza Stark reviewed gene: CP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aceruloplasminaemia, MIM#604290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.115 COX4I2 Zornitza Stark Mode of inheritance for gene: COX4I2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.111 PDIA2 Zornitza Stark Mode of inheritance for gene: PDIA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.109 PDIA2 Zornitza Stark reviewed gene: PDIA2: Rating: RED; Mode of pathogenicity: None; Publications: 20098615; Phenotypes: Bicuspid aortic valve; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.107 COX14 Zornitza Stark Mode of inheritance for gene: COX14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.100 CEP63 Zornitza Stark Mode of inheritance for gene: CEP63 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.97 CDK6 Zornitza Stark Phenotypes for gene: CDK6 were changed from to Microcephaly 12, primary, autosomal recessive, MIM#616080
Mendeliome v0.95 CDK6 Zornitza Stark Mode of inheritance for gene: CDK6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.90 CD96 Zornitza Stark Mode of inheritance for gene: CD96 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.87 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from to Microcephaly 18, primary, autosomal dominant, MIM#617520
Mendeliome v0.85 WDFY3 Zornitza Stark Mode of inheritance for gene: WDFY3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.80 CCDC8 Zornitza Stark Mode of inheritance for gene: CCDC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.79 CCDC8 Zornitza Stark reviewed gene: CCDC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21737058; Phenotypes: 3-M syndrome 3, MIM#614205; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.77 CCDC78 Zornitza Stark Mode of inheritance for gene: CCDC78 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.72 CACNA1G Zornitza Stark Mode of inheritance for gene: CACNA1G was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.64 BDNF Zornitza Stark reviewed gene: BDNF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, congenital, MIM#209880; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.61 ADD3 Zornitza Stark gene: ADD3 was added
gene: ADD3 was added to Mendeliome_VCGS. Sources: Expert list
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 29768408; 23836506
Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3, MIM#617008
Added comment: Four families reported in the literature with bi-allelic variants in this gene causing intellectual disability.
Sources: Expert list
Mendeliome v0.14 KDM6B Zornitza Stark gene: KDM6B was added
gene: KDM6B was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM6B were set to 31124279
Phenotypes for gene: KDM6B were set to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MIM#618505
Review for gene: KDM6B was set to GREEN
Added comment: 12 unrelated patients reported with de novo variants in this gene, no functional evidence.
Sources: Literature
Mendeliome v0.4 ASTN2 Zornitza Stark reviewed gene: ASTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28940097; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.0 MALT1 Zornitza Stark gene: MALT1 was added
gene: MALT1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MALT1 was set to Unknown