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Mendeliome v0.8784 KLK4 Zornitza Stark Phenotypes for gene: KLK4 were changed from to Amelogenesis imperfecta, type IIA1, MIM# 204700
Mendeliome v0.8783 KLK4 Zornitza Stark Publications for gene: KLK4 were set to
Mendeliome v0.8782 KLK4 Zornitza Stark Mode of inheritance for gene: KLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8781 KLK4 Zornitza Stark reviewed gene: KLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 15235027, 23355523, 28611678, 27066511; Phenotypes: Amelogenesis imperfecta, type IIA1, MIM# 204700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8781 ITGB6 Zornitza Stark Marked gene: ITGB6 as ready
Mendeliome v0.8781 ITGB6 Zornitza Stark Gene: itgb6 has been classified as Green List (High Evidence).
Mendeliome v0.8781 ITGB6 Zornitza Stark Classified gene: ITGB6 as Green List (high evidence)
Mendeliome v0.8781 ITGB6 Zornitza Stark Gene: itgb6 has been classified as Green List (High Evidence).
Mendeliome v0.8780 ITGB6 Zornitza Stark gene: ITGB6 was added
gene: ITGB6 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ITGB6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGB6 were set to 25431241; 26695873; 24305999; 24319098
Phenotypes for gene: ITGB6 were set to Amelogenesis imperfecta, type IH, MIM# 616221
Review for gene: ITGB6 was set to GREEN
Added comment: At least 3 unrelated families reported.
Sources: Expert Review
Mendeliome v0.8779 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Mendeliome v0.8779 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Mendeliome v0.8779 STAT3 Zornitza Stark Phenotypes for gene: STAT3 were changed from to Hyper-IgE recurrent infection syndrome MIM# 147060; Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952
Mendeliome v0.8778 STAT3 Zornitza Stark Publications for gene: STAT3 were set to
Mendeliome v0.8777 STAT3 Zornitza Stark Mode of inheritance for gene: STAT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8776 STAT3 Zornitza Stark reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17881745, 14566054, 25349174, 25038750, 25359994; Phenotypes: Hyper-IgE recurrent infection syndrome MIM# 147060, Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8776 STK4 Zornitza Stark Marked gene: STK4 as ready
Mendeliome v0.8776 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
Mendeliome v0.8776 STK4 Zornitza Stark Phenotypes for gene: STK4 were changed from to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868; CD4/CD8 lymphopaenia; cardiac malformations; reduced naïve T cells; increased TEM and TEMRA cells; poor T cell Proliferation; Reduced memory B cells; Reduced IgM, increased IgG, IgA, IgE; impaired antibody responses; intermittent neutropaenia; bacterial/ viral/ fungal infections; autoimmune cytopaenias; mucocutaneous candidiasis; cutaneous warts
Mendeliome v0.8775 STK4 Zornitza Stark Publications for gene: STK4 were set to
Mendeliome v0.8774 STK4 Zornitza Stark Mode of inheritance for gene: STK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8773 SP110 Zornitza Stark Gene: sp110 has been classified as Green List (High Evidence).
Mendeliome v0.8773 SP110 Zornitza Stark Tag founder tag was added to gene: SP110.
Mendeliome v0.8773 SP110 Zornitza Stark Phenotypes for gene: SP110 were changed from to Hepatic veno-occlusive disease with immunodeficiency MIM#235550; Hepatic veno-occlusive disease; susceptibility to Pneumocystis jirovecii pneumonia; cytomegalovirus; thrombocytopaenia; hepatosplenomegaly; cerebrospinal leukodystrophy; memory T/B cell deficiency; low Ig levels; absent tissue plasma cells; absent lymph node germinal centers; hypogammaglobulinaemia
Mendeliome v0.8772 SP110 Zornitza Stark Publications for gene: SP110 were set to
Mendeliome v0.8771 SP110 Zornitza Stark Mode of inheritance for gene: SP110 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8770 SMARCAL1 Zornitza Stark Gene: smarcal1 has been classified as Green List (High Evidence).
Mendeliome v0.8770 SMARCAL1 Zornitza Stark Phenotypes for gene: SMARCAL1 were changed from to Schimke immune-osseous dysplasia MIM# 242900; T cell deficiency; Short stature; spondyloepiphyseal dysplasia; renal dysfunction; lymphocytopaenia; nephropathy; bacterial/viral/fungal infections; may present as SCID; bone marrow failure
Mendeliome v0.8769 SMARCAL1 Zornitza Stark Publications for gene: SMARCAL1 were set to
Mendeliome v0.8768 SMARCAL1 Zornitza Stark Mode of inheritance for gene: SMARCAL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 STK4 Danielle Ariti reviewed gene: STK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22294732, 26117625, 22174160, 22952854; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868, CD4/CD8 lymphopaenia, cardiac malformations, reduced naïve T cells, increased TEM and TEMRA cells, poor T cell Proliferation, Reduced memory B cells, Reduced IgM, increased IgG, IgA, IgE, impaired antibody responses, intermittent neutropaenia, bacterial/ viral/ fungal infections, autoimmune cytopaenias, mucocutaneous candidiasis, cutaneous warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SPINK5 Danielle Ariti reviewed gene: SPINK5: Rating: ; Mode of pathogenicity: None; Publications: 33534181, 20657595; Phenotypes: Netherton syndrome MIM# 256500, Low switched and non-switched B cells, High IgE and IgA, Antibody variably decreased, Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive, food allergies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SP110 Danielle Ariti reviewed gene: SP110: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301448, 31721003; Phenotypes: Hepatic veno-occlusive disease with immunodeficiency MIM#235550, Hepatic veno-occlusive disease, susceptibility to Pneumocystis jirovecii pneumonia, cytomegalovirus, thrombocytopaenia, hepatosplenomegaly, cerebrospinal leukodystrophy, memory T/B cell deficiency, low Ig levels, absent tissue plasma cells, absent lymph node germinal centers, hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 SMARCAL1 Danielle Ariti reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301550, 17089404, 20036229; Phenotypes: Schimke immune-osseous dysplasia MIM# 242900, T cell deficiency, Short stature, spondyloepiphyseal dysplasia, renal dysfunction, lymphocytopaenia, nephropathy, bacterial/viral/fungal infections, may present as SCID, bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8767 GPR68 Zornitza Stark Gene: gpr68 has been classified as Green List (High Evidence).
Mendeliome v0.8767 GPR68 Zornitza Stark Phenotypes for gene: GPR68 were changed from to Amelogenesis imperfecta, hypomaturation type, IIA6 MIM#617217
Mendeliome v0.8766 GPR68 Zornitza Stark Publications for gene: GPR68 were set to
Mendeliome v0.8765 GPR68 Zornitza Stark Mode of inheritance for gene: GPR68 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8764 GPR68 Zornitza Stark reviewed gene: GPR68: Rating: GREEN; Mode of pathogenicity: None; Publications: 27693231, 32279993; Phenotypes: Amelogenesis imperfecta, hypomaturation type, IIA6 MIM#617217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8764 FAM83H Zornitza Stark Gene: fam83h has been classified as Green List (High Evidence).
Mendeliome v0.8764 FAM83H Zornitza Stark Phenotypes for gene: FAM83H were changed from to Amelogenesis imperfecta, type IIIA MIM#130900
Mendeliome v0.8763 FAM83H Zornitza Stark Publications for gene: FAM83H were set to
Mendeliome v0.8762 FAM83H Zornitza Stark Mode of inheritance for gene: FAM83H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8761 FAM83H Zornitza Stark reviewed gene: FAM83H: Rating: GREEN; Mode of pathogenicity: None; Publications: 18484629, 19407157, 19825039, 26481691, 21702852, 20160442, 26142250, 22414746, 19828885, 19220331, 26502894, 18252228, 21597265, 21118793, 26788537, 26171361; Phenotypes: Amelogenesis imperfecta, type IIIA MIM#130900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8761 ENAM Zornitza Stark Gene: enam has been classified as Green List (High Evidence).
Mendeliome v0.8761 ENAM Zornitza Stark Phenotypes for gene: ENAM were changed from to Amelogenesis imperfecta, type IB, MIM# 104500; Amelogenesis imperfecta, type IC, MIM# 204650
Mendeliome v0.8760 ENAM Zornitza Stark Publications for gene: ENAM were set to
Mendeliome v0.8759 ENAM Zornitza Stark Mode of inheritance for gene: ENAM was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8758 ENAM Zornitza Stark reviewed gene: ENAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11487571, 28334996, 14684688, 33864320; Phenotypes: Amelogenesis imperfecta, type IB, MIM# 104500, Amelogenesis imperfecta, type IC, MIM# 204650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8758 FAM20A Zornitza Stark Gene: fam20a has been classified as Green List (High Evidence).
Mendeliome v0.8758 FAM20A Zornitza Stark Phenotypes for gene: FAM20A were changed from to Amelogenesis imperfecta, type IG (enamel-renal syndrome) MIM#204690
Mendeliome v0.8757 FAM20A Zornitza Stark Publications for gene: FAM20A were set to
Mendeliome v0.8756 FAM20A Zornitza Stark Mode of inheritance for gene: FAM20A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8755 FAM20A Zornitza Stark reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23434854, 23697977, 23468644, 24756937, 21549343, 24259279, 24196488, 26502894, 25827751, 21990045; Phenotypes: Amelogenesis imperfecta, type IG (enamel-renal syndrome) MIM#204690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8755 C4orf26 Zornitza Stark Gene: c4orf26 has been classified as Green List (High Evidence).
Mendeliome v0.8755 C4orf26 Zornitza Stark Phenotypes for gene: C4orf26 were changed from to Amelogenesis imperfecta, type IIA4, MIM# 614832
Mendeliome v0.8754 C4orf26 Zornitza Stark Publications for gene: C4orf26 were set to
Mendeliome v0.8753 C4orf26 Zornitza Stark Mode of inheritance for gene: C4orf26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8752 C4orf26 Zornitza Stark reviewed gene: C4orf26: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901946, 27558265; Phenotypes: Amelogenesis imperfecta, type IIA4, MIM# 614832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8752 AMELX Zornitza Stark Gene: amelx has been classified as Green List (High Evidence).
Mendeliome v0.8752 AMELX Zornitza Stark Phenotypes for gene: AMELX were changed from Amelogenesis imperfecta, type 1E, MIM# 301200 to Amelogenesis imperfecta, type 1E, MIM# 301200
Mendeliome v0.8752 AMELX Zornitza Stark Phenotypes for gene: AMELX were changed from to Amelogenesis imperfecta, type 1E, MIM# 301200
Mendeliome v0.8751 AMELX Zornitza Stark Publications for gene: AMELX were set to
Mendeliome v0.8750 AMELX Zornitza Stark Mode of inheritance for gene: AMELX 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 v0.8749 AMELX Zornitza Stark Tag SV/CNV tag was added to gene: AMELX.
Mendeliome v0.8749 AMELX Zornitza Stark reviewed gene: AMELX: Rating: GREEN; Mode of pathogenicity: None; Publications: 17189466, 22243263, 7599636, 23251683, 1483698 1916828, 9188994, 15111628, 11201048, 26502894, 7782077, 11922869, 28130977, 8406474, 11839357, 25117480, 19610109; Phenotypes: Amelogenesis imperfecta, type 1E, MIM# 301200; 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 v0.8749 AMBN Zornitza Stark Gene: ambn has been classified as Green List (High Evidence).
Mendeliome v0.8749 AMBN Zornitza Stark Phenotypes for gene: AMBN were changed from to Amelogenesis imperfecta, type IF MIM#616270
Mendeliome v0.8748 AMBN Zornitza Stark Publications for gene: AMBN were set to
Mendeliome v0.8747 AMBN Zornitza Stark Mode of inheritance for gene: AMBN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8746 AMBN Zornitza Stark reviewed gene: AMBN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24858907, 26502894, 31402633, 30174330; Phenotypes: Amelogenesis imperfecta, type IF MIM#616270; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8746 ACP4 Zornitza Stark reviewed gene: ACP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28513613, 27843125, 33552707; Phenotypes: Amelogenesis imperfecta, type IJ MIM#617297; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8746 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome 38, MIM# 619476
Mendeliome v0.8745 TMEM222 Zornitza Stark Phenotypes for gene: TMEM222 were changed from Intellectual disability; Epilepsy; Microcephaly to Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470; Intellectual disability; Epilepsy; Microcephaly
Mendeliome v0.8744 TMEM222 Zornitza Stark edited their review of gene: TMEM222: Changed phenotypes: Neurodevelopmental disorder with motor and speech delay and behavioural abnormalities, MIM# 619470, Intellectual disability, Epilepsy, Microcephaly
Mendeliome v0.8744 TCF7L2 Zornitza Stark Phenotypes for gene: TCF7L2 were changed from Developmental disorders to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Myopia; Abnormality of skeletal system
Mendeliome v0.8743 TCF7L2 Zornitza Stark Publications for gene: TCF7L2 were set to 33057194
Mendeliome v0.8742 TCF7L2 Zornitza Stark Classified gene: TCF7L2 as Green List (high evidence)
Mendeliome v0.8742 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Green List (High Evidence).
Mendeliome v0.8741 TCF7L2 Zornitza Stark changed review comment from: 2 reviews
Konstantinos Varvagiannis (Other)
I don't know

Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants.

Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11).

One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury.

TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts.

Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development.

Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1].

The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA).

No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism.

There are no variant or other studies performed, nor any animal models discussed.

In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs).

Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm.

There is no other associated phenotype (notably NDD) in OMIM.
G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF).
SysID includes this gene within the autism candidate genes and current primary ID genes.; to: Dias et al (2021 - PMID: 34003604) describe the phenotype of 11 unrelated individuals harboring de novo missense/truncating TCF7L2 variants.

Features included DD in childhood (motor delay in 8/11, speech delay in 11/11), intellectual abilities ranging from average cognitive functioning to mild/moderate ID (the latter observed in 5/11), myopia (6/11) , dysmorphic features, variable orthopedic findings, and neuropsychiatric comorbidities incl. ASD (4/11) / ADHD (4/11).

One additional (12th) individual was excluded from this summary due to concurrent diagnosis of hypoxic-ischemic injury.

TCF7L2 on 10q25 encodes transcription factor 7-like 2, a high mobility group (HMG) box-containing transcription factor. As the authors discuss, the protein mediates canonical Wnt signaling. Secreted Wnt proteins lead to release of beta-catenin (CTNNB1) which after translocation to the nucleus acts with DNA-binding factors incl. TCF7L2 to turn on Wnt-responsive target genes. As a result TCF7L2 acts with beta-catenin as a switch for transcriptional regulation. Multiple alternative spliced TCF7L2 transcripts mediate it's function and specificity of transcriptional repertoire in a variety of tissues and contexts.

Dias et al provide references for its role in nervous system development incl. neurogenesis and thalamic development.

Variants in all cases occurred as de novo events with pLoF (stopgain, frameshift, splicing) ones predicted to lead to NMD. Missense variants occurred in all cases in or adjacent to the HMG box domain [aa 350-417]. 5 different missense variants affecting 3 residues were reported incl. c.1142A>C, c.1143C>G (leading to Asn381Thr/Lys respectively), c.1250G>T (Trp417Leu), c.1267T>C, c.1268A>G (leading to Tyr423His/Cys) [NM_001146274.1].

The gene has a pLI of 0.99-1 gnomAD/ExAC while there is a region of missense constraint encompassing the HMG box domain (the latter is an evolutionary conserved region mediating interactions with DNA).

No phenotypic differences were observed among individuals with pLoF and missense SNVs, and haploinsufficiency is presumed to be the underlying mechanism.

There are no variant or other studies performed, nor any animal models discussed.

In supplementary table 2, the authors provide several references to previous large scale sequencing studies with brief/incomplete descriptions of individuals de novo TCF7L2 variants and neurodevelopmental disorder (ID/ASD - Iossifov, De Rubeis, Lelieveld, McRae/DDD study and many other Refs).

Heterozygous TCF7L2 variants are thought to confer susceptibility to type diabetes mellitus (MIM 125853). Individuals reported by Dias et al did not have endocrine abnormalities including DM. A study by Roychowdhury et al (2021 - PMID: 34265237) suggests that regulatory variants in TCF7L2 are associated with thoracic aneurysm.

There is no other associated phenotype (notably NDD) in OMIM.
G2P includes TCF7L2 in its DD panel (Disease : TC7L2-related DD, Confidence:confirmed, Monoallelic, LoF).
SysID includes this gene within the autism candidate genes and current primary ID genes.
Mendeliome v0.8741 TCF7L2 Zornitza Stark reviewed gene: TCF7L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34003604; Phenotypes: Global developmental delay, Intellectual disability, Autism, Attention deficit hyperactivity disorder, Myopia, Abnormality of skeletal system; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8741 LTBP3 Zornitza Stark Marked gene: LTBP3 as ready
Mendeliome v0.8741 LTBP3 Zornitza Stark Gene: ltbp3 has been classified as Green List (High Evidence).
Mendeliome v0.8741 LTBP3 Zornitza Stark Phenotypes for gene: LTBP3 were changed from to Dental anomalies and short stature, MIM# 601216; Geleophysic dysplasia 3, MIM# 617809; Thoracic aneurysm
Mendeliome v0.8740 LTBP3 Zornitza Stark Publications for gene: LTBP3 were set to
Mendeliome v0.8739 LTBP3 Zornitza Stark Mode of inheritance for gene: LTBP3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8738 LTBP3 Zornitza Stark reviewed gene: LTBP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19344874, 25899461, 25669657, 29625025, 27068007, 34150014; Phenotypes: Dental anomalies and short stature, MIM# 601216, Geleophysic dysplasia 3, MIM# 617809, Thoracic aneurysm; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8738 ARIH1 Zornitza Stark reviewed gene: ARIH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8738 ARIH1 Zornitza Stark Mode of inheritance for gene: ARIH1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8737 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Mendeliome v0.8737 PIDD1 Zornitza Stark Classified gene: PIDD1 as Green List (high evidence)
Mendeliome v0.8737 PIDD1 Zornitza Stark Gene: pidd1 has been classified as Green List (High Evidence).
Mendeliome v0.8736 PIDD1 Zornitza Stark gene: PIDD1 was added
gene: PIDD1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to 28397838; 29302074; 33414379; 34163010
Phenotypes for gene: PIDD1 were set to Global developmental delay; Intellectual disability; Seizures; Autism; Behavioral abnormality; Psychosis; Pachygyria; Lissencephaly; Abnormality of the corpus callosum
Review for gene: PIDD1 was set to GREEN
Added comment: There is enough evidence to include this gene in the current panel with green rating.

Biallelic PIDD1 pathogenic variants have been reported in 26 individuals (11 families) with DD (all), variable degrees of ID (mild to severe), behavioral (eg. aggression/self-mutilation in several, ADHD) and/or psychiatric abnormalities (ASD, psychosis in 5 belonging to 3 families), well-controlled epilepsy is some (9 subjects from 6 families) and MRI abnormalities notably abnormal gyration pattern (pachygyria with predominant anterior gradient) as well as corpus callosum anomalies (commonly thinning) in several. Dysmorphic features have been reported in almost all, although there has been no specific feature suggested.

The first reports on the phenotype associated with biallelic PIDD1 mutations were made by Harripaul et al (2018 - PMID: 28397838) and Hu et al (2019 - PMID: 29302074) [both studies investigating large cohorts of individuals with ID from consanguineous families].

Sheikh et al (2021 - PMID: 33414379) provided details on the phenotype of 15 individuals from 5 families including those from the previous 2 reports and studied provided evidence on the role of PIDD1 and the effect of variants.

Zaki et al (2021 - PMID: 34163010) reported 11 additional individuals from 6 consanguineous families, summarize the features of all subjects published in the literature and review the neuroradiological features of the disorder.

PIDD1 encodes p53-induced death domain protein 1. The protein is part of the PIDDosome, a multiprotein complex also composed of the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 and induces apoptosis in response to DNA damage.

There are 5 potential PIDD1 mRNA transcript variants with NM_145886.4 corresponding to the longest. Similar to the protein encoded by CRADD, PIDD1 contains a death domain (DD - aa 774-893). Constitutive post-translational processing gives PIDD1-N, PIDD1-C the latter further processed into PIDD1-CC (by auto-cleavage). Serine residues at pos. 446 and 588 are involved in this autoprocessing generating PIDD1-C (aa 446-910) and PIDD1-CC (aa 774-893). The latter is needed for caspase-2 activation.

Most (if not all) individuals belonged to consanguineous families of different origins and harbored pLoF or missense variants.

Variants reported so far include : c.2587C>T; p.Gln863* / c.1909C>T ; p.Arg637* / c.2443C>T / p.Arg815Trp / c.2275-1G>A which upon trap assay was shown to lead to skipping of ex15 with direct splicing form exon14 to the terminal exon 16 (resulting to p.Arg759Glyfs*1 with exlcusion of the entire DD) / c.2584C>T; p.Arg862Trp / c.1340G>A; p.Trp447* / c.2116_2120del; p.Val706His*, c.1564_1565del; p.Gly602fs*26

Evidence so far provided includes:
- Biallelic CRADD variants cause a NDD disorder and a highly similar gyration pattern.
- Confirmation of splicing effect (eg. for c.2275-1G>A premature stop in position 760) or poor expression (NM_145886.3:c.2587C>T; p.Gln863*). Arg815Trp did not affect autoprocessing or protein stability.
- Abnormal localization pattern, loss of interaction with CRADD and failure to activate caspase-2 (MDM2 cleavage assay) [p.Gln863* and Arg815Trp]
- Available expression data from GTEx (PIDD1 having broad expression in multiple tissues, but higher in brain cerebellum) as well as BrainSpan and PsychEncode studies suggesting high coexpression of PIDD1, CRADD and CASP2 in many regions in the developing human brain.
- Variants in other genes encoding proteins interacting with PIDD1 (MADD, FADD, DNAJ, etc) are associated with NDD.

Pidd-1 ko mice (ex3-15 removal) lack however CNS-related phenotypes. These show decreased anxiety but no motor anomalies. This has also been the case with Cradd-/- mice displaying no significant CNS phenotypes without lamination defects.

There is currently no associated phenotype in OMIM. PIDD1 is listed in the DD panel of G2P (PIDD1-related NDD / biallelic / loss of function / probable) . SysID includes PIDD1 among the current primary ID genes.
Sources: Expert Review
Mendeliome v0.8735 COLGALT1 Bryony Thompson Marked gene: COLGALT1 as ready
Mendeliome v0.8735 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Mendeliome v0.8735 COLGALT1 Bryony Thompson Classified gene: COLGALT1 as Green List (high evidence)
Mendeliome v0.8735 COLGALT1 Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence).
Mendeliome v0.8734 COLGALT1 Bryony Thompson gene: COLGALT1 was added
gene: COLGALT1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980
Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360
Review for gene: COLGALT1 was set to GREEN
Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos.
Sources: Other
Mendeliome v0.8733 JAKMIP1 Seb Lunke Gene: jakmip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8733 JAKMIP1 Seb Lunke Classified gene: JAKMIP1 as Amber List (moderate evidence)
Mendeliome v0.8733 JAKMIP1 Seb Lunke Gene: jakmip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8732 JAKMIP1 Seb Lunke gene: JAKMIP1 was added
gene: JAKMIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: JAKMIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JAKMIP1 were set to 29158550; 26627310; 27799067
Phenotypes for gene: JAKMIP1 were set to Intellectual disability; Seizures
Review for gene: JAKMIP1 was set to AMBER
Added comment: Identified in two independent patients in the literature with a mouse model.

Patient 1 (27799067) with developmental delay, speech delay, and cognitive impairment; self-injurious and aggressive behaviour, seizures, dysmorphic features. De-novo missense JAKMIP1 (p.D586H).

Patient 2 (29158550) with feeding difficulties, hypotonia, epilepsy, severe ID, no active speech, kyphoscoliosis, constipation, autism, short stature. Splice variant c.1432-2A>G, no segregation or RNA data available.

KO mouse model (27799067) displays social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors.
Sources: Literature
Mendeliome v0.8731 ARIH1 Bryony Thompson Gene: arih1 has been classified as Green List (High Evidence).
Mendeliome v0.8731 ARIH1 Bryony Thompson Classified gene: ARIH1 as Green List (high evidence)
Mendeliome v0.8731 ARIH1 Bryony Thompson Gene: arih1 has been classified as Green List (High Evidence).
Mendeliome v0.8730 ARIH1 Bryony Thompson gene: ARIH1 was added
gene: ARIH1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: ARIH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARIH1 were set to 29689197; 32102558
Phenotypes for gene: ARIH1 were set to Thoracic aortic aneurysm
Review for gene: ARIH1 was set to GREEN
Added comment: 3 unrelated families: A de novo case (R171*) with thoracic aortic aneurysm (TAA), and 2 siblings with TAA and a missense (E15Q). Another proband with cerebrovascular aneurysm (family history of TAA) and a missense variant (E44G). Supporting functional assays of the variants and a drosophila model.
Sources: Other
Mendeliome v0.8729 SLC41A1 Zornitza Stark Phenotypes for gene: SLC41A1 were changed from Nephronophthisis to Nephronophthisis-like nephropathy 2, MIM# 619468
Mendeliome v0.8728 SLC41A1 Zornitza Stark edited their review of gene: SLC41A1: Changed phenotypes: Nephronophthisis-like nephropathy 2, MIM# 619468
Mendeliome v0.8728 PRPF31 Zornitza Stark Gene: prpf31 has been classified as Green List (High Evidence).
Mendeliome v0.8728 PRPF31 Zornitza Stark Phenotypes for gene: PRPF31 were changed from to Retinitis pigmentosa 11, MIM#600138
Mendeliome v0.8727 PRPF31 Zornitza Stark Publications for gene: PRPF31 were set to
Mendeliome v0.8726 PRPF31 Zornitza Stark Mode of inheritance for gene: PRPF31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8725 PRPF31 Zornitza Stark Tag SV/CNV tag was added to gene: PRPF31.
Mendeliome v0.8725 PRPF31 Zornitza Stark reviewed gene: PRPF31: Rating: GREEN; Mode of pathogenicity: None; Publications: 32014492; Phenotypes: Retinitis pigmentosa 11, MIM#600138; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8725 RNF168 Zornitza Stark Gene: rnf168 has been classified as Green List (High Evidence).
Mendeliome v0.8725 RNF168 Zornitza Stark Phenotypes for gene: RNF168 were changed from to RIDDLE syndrome MIM# 611943; Radiosensitivity; Immune Deficiency; Dysmorphic Features; Learning difficulties; Low IgG or IgA; Short stature; mild defect of motor control to ataxia; normal intelligence to learning difficulties; mild facial dysmorphism to microcephaly
Mendeliome v0.8724 RNF168 Zornitza Stark Publications for gene: RNF168 were set to
Mendeliome v0.8723 RNF168 Zornitza Stark Mode of inheritance for gene: RNF168 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8722 RFXAP Zornitza Stark Gene: rfxap has been classified as Green List (High Evidence).
Mendeliome v0.8722 RFXAP Zornitza Stark Phenotypes for gene: RFXAP were changed from to Bare lymphocyte syndrome, type II, complementation group D MIM# 209920; Low CD4+ T cells; reduced MHC II expression on lymphocytes; Normal-low Ig levels; Failure to thrive; respiratory/gastrointestinal infections; liver/biliary tract disease; diarrhoea; Severe autoimmune cytopaenia; agammaglobulinaemia
Mendeliome v0.8721 RFXAP Zornitza Stark Publications for gene: RFXAP were set to
Mendeliome v0.8720 RFXAP Zornitza Stark Mode of inheritance for gene: RFXAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8719 RFXAP Zornitza Stark Tag founder tag was added to gene: RFXAP.
Mendeliome v0.8719 RFXANK Zornitza Stark Gene: rfxank has been classified as Green List (High Evidence).
Mendeliome v0.8719 RFXANK Zornitza Stark Phenotypes for gene: RFXANK were changed from to MHC class II deficiency, complementation group B MIM# 209920; Bare Lymphocyte Syndrome, type II, complementation group B; Low CD4+ T cells; reduced MHC II expression on lymphocytes; Normal-low Ig levels; Failure to thrive; respiratory/gastrointestinal infections; liver/biliary tract disease; diarrhoea; Severe autoimmune cytopaenia; agammaglobulinaemia
Mendeliome v0.8718 RFXANK Zornitza Stark Publications for gene: RFXANK were set to
Mendeliome v0.8717 RFXANK Zornitza Stark Tag founder tag was added to gene: RFXANK.
Mendeliome v0.8717 RFXANK Zornitza Stark Mode of inheritance for gene: RFXANK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8716 RBCK1 Zornitza Stark Gene: rbck1 has been classified as Green List (High Evidence).
Mendeliome v0.8716 RBCK1 Zornitza Stark Phenotypes for gene: RBCK1 were changed from to Polyglucosan body myopathy 1 with or without immunodeficiency MIM# 615895; muscular weakness; cardiomyopathy; recurrent bacterial/viral infections; autoinflammation; immunodeficiency; Poor antibody responses to polysaccharides; failure to thrive; fever; pneumonia
Mendeliome v0.8715 RBCK1 Zornitza Stark Publications for gene: RBCK1 were set to
Mendeliome v0.8714 RBCK1 Zornitza Stark Mode of inheritance for gene: RBCK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RFXANK Danielle Ariti reviewed gene: RFXANK: Rating: GREEN; Mode of pathogenicity: None; Publications: 12618906; Phenotypes: MHC class II deficiency, complementation group B MIM# 209920, Bare Lymphocyte Syndrome, type II, complementation group B, Low CD4+ T cells, reduced MHC II expression on lymphocytes, Normal-low Ig levels, Failure to thrive, respiratory/gastrointestinal infections, liver/biliary tract disease, diarrhoea, Severe autoimmune cytopaenia, agammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RFXAP Danielle Ariti reviewed gene: RFXAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9118943, 32875002, 11258423; Phenotypes: Bare lymphocyte syndrome, type II, complementation group D MIM# 209920, Low CD4+ T cells, reduced MHC II expression on lymphocytes, Normal-low Ig levels, Failure to thrive, respiratory/gastrointestinal infections, liver/biliary tract disease, diarrhoea, Severe autoimmune cytopaenia, agammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RNF168 Danielle Ariti reviewed gene: RNF168: Rating: GREEN; Mode of pathogenicity: None; Publications: 19203578, 21394101, 29255463, 21552324; Phenotypes: RIDDLE syndrome MIM# 611943, Radiosensitivity, Immune Deficiency, Dysmorphic Features, Learning difficulties, Low IgG or IgA, Short stature, mild defect of motor control to ataxia, normal intelligence to learning difficulties, mild facial dysmorphism to microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 RBCK1 Danielle Ariti reviewed gene: RBCK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29260357, 29695863; Phenotypes: Polyglucosan body myopathy 1 with or without immunodeficiency MIM# 615895, muscular weakness, cardiomyopathy, recurrent bacterial/viral infections, autoinflammation, immunodeficiency, Poor antibody responses to polysaccharides, failure to thrive, fever, pneumonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 ABCC2 Zornitza Stark Gene: abcc2 has been classified as Green List (High Evidence).
Mendeliome v0.8713 ABCC2 Zornitza Stark Phenotypes for gene: ABCC2 were changed from to Dubin-Johnson syndrome, MIM# 237500
Mendeliome v0.8712 ABCC2 Zornitza Stark Mode of inheritance for gene: ABCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8711 ABCC2 Zornitza Stark reviewed gene: ABCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dubin-Johnson syndrome, MIM# 237500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8711 CLDN9 Bryony Thompson Publications for gene: CLDN9 were set to 31175426; 19696885
Mendeliome v0.8710 CLDN9 Bryony Thompson Classified gene: CLDN9 as Green List (high evidence)
Mendeliome v0.8710 CLDN9 Bryony Thompson Gene: cldn9 has been classified as Green List (High Evidence).
Mendeliome v0.8709 CLDN9 Bryony Thompson reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19696885, 31175426, 34265170; Phenotypes: Deafness, autosomal recessive 116 MIM#619093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8709 UBR1 Zornitza Stark changed review comment from: >50 unrelated families reported, reviewed in PMID: 24599544.

Common clinical features include poor growth, mental retardation, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency.; to: >50 unrelated families reported, reviewed in PMID: 24599544.

Common clinical features include poor growth, intellectual disability, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency.
Mendeliome v0.8709 UBR1 Zornitza Stark Gene: ubr1 has been classified as Green List (High Evidence).
Mendeliome v0.8709 UBR1 Zornitza Stark Phenotypes for gene: UBR1 were changed from to Johanson-Blizzard syndrome (MIM#243800)
Mendeliome v0.8708 UBR1 Zornitza Stark Publications for gene: UBR1 were set to
Mendeliome v0.8707 UBR1 Zornitza Stark Mode of inheritance for gene: UBR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8706 UBR1 Zornitza Stark reviewed gene: UBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24599544; Phenotypes: Johanson-Blizzard syndrome (MIM#243800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8706 ACTL6A Zornitza Stark Marked gene: ACTL6A as ready
Mendeliome v0.8706 ACTL6A Zornitza Stark Gene: actl6a has been classified as Green List (High Evidence).
Mendeliome v0.8706 ACTL6A Zornitza Stark Phenotypes for gene: ACTL6A were changed from to Intellectual disability
Mendeliome v0.8705 ACTL6A Zornitza Stark Publications for gene: ACTL6A were set to
Mendeliome v0.8704 ACTL6A Zornitza Stark Mode of inheritance for gene: ACTL6A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8703 ACTL6A Zornitza Stark changed review comment from: Two individuals from unrelated families reported with missense variants in this gene. Part of the BAF complex. Only one confirmed de novo.; to: Two individuals from unrelated families reported with missense variants in this gene, and one with a splice-site variant. Part of the BAF complex. Only one missense confirmed de novo, pathogenicity of the other variant uncertain.
PMID 31994175: fourth individual reported, recurrent de novo p.Arg377Trp
Mendeliome v0.8703 ACTL6A Zornitza Stark edited their review of gene: ACTL6A: Changed publications: 28649782, 31994175
Mendeliome v0.8703 VAV1 Zornitza Stark Gene: vav1 has been classified as Red List (Low Evidence).
Mendeliome v0.8703 VAV1 Zornitza Stark gene: VAV1 was added
gene: VAV1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: VAV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAV1 were set to 20638113; 23058036
Phenotypes for gene: VAV1 were set to Common variable immnodeficiency
Review for gene: VAV1 was set to RED
Added comment: Reduced VAV1 expression has been reported in multiple T-CVID cases, however only one large deletion (exon 2-27) has been reported in a single case in a publication from 2012. The CNV was detected using real-time qPCR, but was not confirmed by an orthogonal method.
Sources: Expert Review
Mendeliome v0.8702 TCF3 Zornitza Stark Marked gene: TCF3 as ready
Mendeliome v0.8702 TCF3 Zornitza Stark Gene: tcf3 has been classified as Green List (High Evidence).
Mendeliome v0.8702 TCF3 Zornitza Stark Phenotypes for gene: TCF3 were changed from to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941
Mendeliome v0.8701 TCF3 Zornitza Stark Publications for gene: TCF3 were set to
Mendeliome v0.8700 TCF3 Zornitza Stark Mode of inheritance for gene: TCF3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8699 TCF3 Zornitza Stark reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24216514, 28532655, 30063982, 8001124, 8001125; Phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8699 PRKCD Zornitza Stark Gene: prkcd has been classified as Green List (High Evidence).
Mendeliome v0.8699 PRKCD Zornitza Stark Phenotypes for gene: PRKCD were changed from to Autoimmune lymphoproliferative syndrome, type III, MIM# 615559; CVID 9
Mendeliome v0.8698 PRKCD Zornitza Stark Publications for gene: PRKCD were set to
Mendeliome v0.8697 PRKCD Zornitza Stark Mode of inheritance for gene: PRKCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8696 PRKCD Zornitza Stark reviewed gene: PRKCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23319571, 23666743, 23430113, 11976687, 33047643, 29867916; Phenotypes: Autoimmune lymphoproliferative syndrome, type III, MIM# 615559, CVID 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8696 CD19 Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Clinical features include increased susceptibility to infection, hypogammaglobulinaemia, and normal numbers of mature B cells in blood, indicating a B-cell antibody-deficient immunodeficiency disorder.
Mendeliome v0.8696 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
Mendeliome v0.8696 CD19 Zornitza Stark Phenotypes for gene: CD19 were changed from to Immunodeficiency, common variable, 3, MIM# 613493
Mendeliome v0.8695 CD19 Zornitza Stark Publications for gene: CD19 were set to
Mendeliome v0.8694 CD19 Zornitza Stark Mode of inheritance for gene: CD19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8693 CD19 Zornitza Stark reviewed gene: CD19: Rating: GREEN; Mode of pathogenicity: None; Publications: 16672701, 17882224, 17882224, 21330302, 21159371; Phenotypes: Immunodeficiency, common variable, 3, MIM# 613493; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8693 SNRPB Zornitza Stark Gene: snrpb has been classified as Green List (High Evidence).
Mendeliome v0.8693 SNRPB Zornitza Stark Phenotypes for gene: SNRPB were changed from to Cerebrocostomandibular syndrome, MIM# 117650
Mendeliome v0.8692 SNRPB Zornitza Stark Publications for gene: SNRPB were set to
Mendeliome v0.8691 SNRPB Zornitza Stark Mode of inheritance for gene: SNRPB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8690 SNRPB Zornitza Stark Tag 5'UTR tag was added to gene: SNRPB.
Tag deep intronic tag was added to gene: SNRPB.
Mendeliome v0.8690 SNRPB Zornitza Stark reviewed gene: SNRPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25047197, 25504470, 26971886; Phenotypes: Cerebrocostomandibular syndrome, MIM# 117650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8690 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Mendeliome v0.8690 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, MIM# 311900
Mendeliome v0.8689 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Mendeliome v0.8688 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8687 RBM10 Zornitza Stark reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20451169, 24259342, 30450804, 30189253, 33340101; Phenotypes: TARP syndrome, MIM# 311900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8687 IPO8 Zornitza Stark Phenotypes for gene: IPO8 were changed from Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities to Vascular aneurysm, immune dysregulation, skeletal anomalies, and skin and joint laxity, MIM# 619472; Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities
Mendeliome v0.8686 IPO8 Zornitza Stark edited their review of gene: IPO8: Changed phenotypes: Vascular aneurysm, immune dysregulation, skeletal anomalies, and skin and joint laxity, MIM# 619472, Loeys-Dietz syndrome-like, cardiovascular, neurologic, skeletal and immunologic abnormalities
Mendeliome v0.8686 OTX2 Zornitza Stark edited their review of gene: OTX2: Added comment: Three families reported with variants in OTX2 and otocyephaly-dysgnathia. Note variants were inherited in two of the families: in one family, from mother with microphthalmia (recognised OTX2 phenotype) and the other from an unaffected father. Lamb animal model reported.; Changed publications: 24167467, 25589041, 31969185; Changed phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125, Otocephaly-dysgnathia complex
Mendeliome v0.8686 POLR1D Zornitza Stark Gene: polr1d has been classified as Green List (High Evidence).
Mendeliome v0.8686 POLR1D Zornitza Stark Phenotypes for gene: POLR1D were changed from to Treacher Collins syndrome 2, MIM# 613717
Mendeliome v0.8685 POLR1D Zornitza Stark Publications for gene: POLR1D were set to
Mendeliome v0.8684 POLR1D Zornitza Stark Mode of inheritance for gene: POLR1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8683 POLR1D Zornitza Stark reviewed gene: POLR1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 24603435, 27448281, 25790162; Phenotypes: Treacher Collins syndrome 2, MIM# 613717; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8683 TP73 Zornitza Stark Phenotypes for gene: TP73 were changed from Cortical malformation; Lissencephaly to Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Cortical malformation; Lissencephaly
Mendeliome v0.8682 TP73 Zornitza Stark reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 47, and lissencephaly, MIM#619466; Mode of inheritance: None
Mendeliome v0.8682 SYT2 Zornitza Stark Phenotypes for gene: SYT2 were changed from Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040 to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Mendeliome v0.8681 SYT2 Zornitza Stark edited their review of gene: SYT2: Changed phenotypes: Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040, Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Mendeliome v0.8681 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Mendeliome v0.8681 POLR1C Zornitza Stark Phenotypes for gene: POLR1C were changed from to Treacher Collins syndrome 3, MIM# 248390; Leukodystrophy, hypomyelinating, 11, MIM# 616494
Mendeliome v0.8680 POLR1C Zornitza Stark Publications for gene: POLR1C were set to
Mendeliome v0.8679 POLR1C Zornitza Stark Mode of inheritance for gene: POLR1C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 POLR1C Zornitza Stark reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131976, 30957429, 26151409, 32042905; Phenotypes: Treacher Collins syndrome 3, MIM# 248390, Leukodystrophy, hypomyelinating, 11, MIM# 616494; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8678 SF3B4 Zornitza Stark Gene: sf3b4 has been classified as Green List (High Evidence).
Mendeliome v0.8678 SF3B4 Zornitza Stark Phenotypes for gene: SF3B4 were changed from to Acrofacial dysostosis 1, Nager type, MIM# 154400
Mendeliome v0.8677 SF3B4 Zornitza Stark Publications for gene: SF3B4 were set to
Mendeliome v0.8676 SF3B4 Zornitza Stark Mode of inheritance for gene: SF3B4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 SF3B4 Zornitza Stark reviewed gene: SF3B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541558, 23568615, 24003905; Phenotypes: Acrofacial dysostosis 1, Nager type, MIM# 154400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8675 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Mendeliome v0.8675 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Mendeliome v0.8675 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Mendeliome v0.8674 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Mendeliome v0.8673 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8672 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 17351359, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8672 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from Hand and foot malformations to Hand and foot malformations; Hirschsprung disease
Mendeliome v0.8671 SPTBN4 Zornitza Stark reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33772159, 29861105; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, MIM# 617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8671 RGS10 Zornitza Stark Gene: rgs10 has been classified as Red List (Low Evidence).
Mendeliome v0.8671 RGS10 Zornitza Stark gene: RGS10 was added
gene: RGS10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RGS10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RGS10 were set to 34315806; 34339853
Phenotypes for gene: RGS10 were set to Immunodeficiency; short stature
Review for gene: RGS10 was set to RED
Added comment: Three affected siblings with short stature and immunodeficiency and segregating biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals had recurrent infections, hypergammaglobulinaemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Limited functional data presented. Further experimental data linking RGS10 to immune function presented in PMID 34339853.
Sources: Literature
Mendeliome v0.8670 MAST3 Zornitza Stark Marked gene: MAST3 as ready
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Mendeliome v0.8670 MAST3 Zornitza Stark Classified gene: MAST3 as Green List (high evidence)
Mendeliome v0.8670 MAST3 Zornitza Stark Gene: mast3 has been classified as Green List (High Evidence).
Mendeliome v0.8669 MAST3 Zornitza Stark gene: MAST3 was added
gene: MAST3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST3 were set to 34185323
Phenotypes for gene: MAST3 were set to Developmental and epileptic encephalopathy
Review for gene: MAST3 was set to GREEN
Added comment: Eleven individuals reported with de novo missense variants in the STK domain, including two recurrent variants p.G510S (n = 5) and p.G515S (n = 3). All 11 individuals had developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at <2 years of age. All patients developed multiple seizure types, 9 of 11 patients had seizures triggered by fever and 9 of 11 patients had drug-resistant seizures. Limited functional data.
Sources: Literature
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8668 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Mendeliome v0.8668 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Mendeliome v0.8667 SF3B2 Zornitza Stark gene: SF3B2 was added
gene: SF3B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Mendeliome v0.8666 IMPG1 Zornitza Stark Gene: impg1 has been classified as Green List (High Evidence).
Mendeliome v0.8666 IMPG1 Zornitza Stark Phenotypes for gene: IMPG1 were changed from to Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8665 IMPG1 Zornitza Stark Publications for gene: IMPG1 were set to
Mendeliome v0.8664 IMPG1 Zornitza Stark Mode of inheritance for gene: IMPG1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8663 IMPG1 Arina Puzriakova reviewed gene: IMPG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23993198, 28644393, 30589393, 30688845, 32817297; Phenotypes: Macular dystrophy, vitelliform, 4, OMIM:616151, Retinitis pigmentosa, MONDO:0019200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8663 IFT172 Zornitza Stark Phenotypes for gene: IFT172 were changed from Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome to Retinitis pigmentosa 71 616394; Short-rib thoracic dysplasia 10 with or without polydactyly - 615630; Bardet-Biedl syndrome 20, MIM# 619471
Mendeliome v0.8662 TRIM8 Zornitza Stark Phenotypes for gene: TRIM8 were changed from Intellectual disability; Seizures to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428; Intellectual disability; Seizures
Mendeliome v0.8661 TRIM8 Zornitza Stark edited their review of gene: TRIM8: Changed phenotypes: Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428, Intellectual disability, Seizures
Mendeliome v0.8661 CUL7 Zornitza Stark Gene: cul7 has been classified as Green List (High Evidence).
Mendeliome v0.8661 CUL7 Zornitza Stark Phenotypes for gene: CUL7 were changed from to 3-M syndrome 1, MIM# 273750; Yakut short stature syndrome
Mendeliome v0.8660 CUL7 Zornitza Stark Publications for gene: CUL7 were set to
Mendeliome v0.8659 CUL7 Zornitza Stark Mode of inheritance for gene: CUL7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8658 CUL7 Zornitza Stark reviewed gene: CUL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16142236, 19225462, 17675530; Phenotypes: 3-M syndrome 1, MIM# 273750, Yakut short stature syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8658 ACAN Zornitza Stark Publications for gene: ACAN were set to
Mendeliome v0.8657 ACAN Zornitza Stark edited their review of gene: ACAN: Added comment: Patients with SSOAD exhibit a broad phenotypic spectrum involving short stature associated with advanced bone maturation and early-onset osteoarthritis (OA), as well as mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disc disease and osteochondritis dissecans, which is characterized by separation of articular cartilage and subchondral bone from the articular surface. Phenotypes are highly variable even among patients within the same family, and there are no apparent genotype-phenotype correlations.

Well established gene-disease association, multiple families reported.

Note fewer families reported with bi-allelic variants in this gene and extreme short stature.; Changed publications: 24762113, 27870580, 19110214, 30124491, 28331218, 20137779; Changed phenotypes: Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800, Spondyloepimetaphyseal dysplasia, aggrecan type 612813
Mendeliome v0.8657 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Mendeliome v0.8657 NFKBIA Zornitza Stark Phenotypes for gene: NFKBIA were changed from to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132; Ectodermal dysplasia; TCR/ BCR activation impaired; low memory and isotype switched B cells; decreased IgG and IgA; elevated IgM; poor specific antibody responses; diarrhoea; agammaglobulinaemia; ectodermal dysplasia; recurrent respiratory and gastrointestinal infections; colitis; variable defects of skin, hair and teeth
Mendeliome v0.8656 NFKBIA Zornitza Stark Mode of pathogenicity for gene: NFKBIA was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.8655 NFKBIA Zornitza Stark Mode of inheritance for gene: NFKBIA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8654 NFKB2 Zornitza Stark Gene: nfkb2 has been classified as Green List (High Evidence).
Mendeliome v0.8654 NFKB2 Zornitza Stark Phenotypes for gene: NFKB2 were changed from to Immunodeficiency, common variable, 10 MIM# 615577; Low serum IgG, IgA, IgM; low B cell numbers; low switched memory B cells; Recurrent sinopulmonary infections, Alopecia; endocrinopathies; ACTH deficiency
Mendeliome v0.8653 NFKB2 Zornitza Stark Publications for gene: NFKB2 were set to
Mendeliome v0.8652 NFKB2 Zornitza Stark Mode of inheritance for gene: NFKB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8651 NFKB1 Zornitza Stark Gene: nfkb1 has been classified as Green List (High Evidence).
Mendeliome v0.8651 NFKB1 Zornitza Stark Phenotypes for gene: NFKB1 were changed from to Immunodeficiency, common variable, 12 MIM# 616576; Normal-low IgG, IgA, IgM; low-normal B cells; low switched memory B cells; hypogammaglobulinaemia; recurrent respiratory and gastrointestinal infections; Chronic obstructive pulmonary disease COPD; EBV proliferation; autoimmunity; alopecia
Mendeliome v0.8650 NFKB1 Zornitza Stark Publications for gene: NFKB1 were set to
Mendeliome v0.8649 NFKB1 Zornitza Stark Mode of inheritance for gene: NFKB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8648 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8648 MCM4 Zornitza Stark Phenotypes for gene: MCM4 were changed from to Immunodeficiency 54 MIM# 609981; Decreased NK cell number and function; Viral infections (EBV, HSV, VZV); Short stature; B cell lymphoma; Adrenal failure; Failure to thrive; Microcephaly; Increased chromosomal breakage; Hyperpigmentation; Lymphadenopathy
Mendeliome v0.8647 MCM4 Zornitza Stark Publications for gene: MCM4 were set to
Mendeliome v0.8646 MCM4 Zornitza Stark Mode of inheritance for gene: MCM4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8645 MCM4 Zornitza Stark Classified gene: MCM4 as Amber List (moderate evidence)
Mendeliome v0.8645 MCM4 Zornitza Stark Gene: mcm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8644 MCM4 Zornitza Stark Tag founder tag was added to gene: MCM4.
Mendeliome v0.8644 MCM4 Zornitza Stark reviewed gene: MCM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54 MIM# 609981, Decreased NK cell number and function, Viral infections (EBV, HSV, VZV), Short stature, B cell lymphoma, Adrenal failure, Failure to thrive, Microcephaly, Increased chromosomal breakage, Hyperpigmentation, Lymphadenopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8644 MAP3K14 Zornitza Stark Gene: map3k14 has been classified as Green List (High Evidence).
Mendeliome v0.8644 MAP3K14 Zornitza Stark Phenotypes for gene: MAP3K14 were changed from to NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels
Mendeliome v0.8643 MAP3K14 Zornitza Stark Publications for gene: MAP3K14 were set to
Mendeliome v0.8642 MAP3K14 Zornitza Stark Mode of inheritance for gene: MAP3K14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 MAP3K14 Zornitza Stark reviewed gene: MAP3K14: Rating: GREEN; Mode of pathogenicity: None; Publications: 10319865, 11238593, 12352969; Phenotypes: NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8641 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Mendeliome v0.8641 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from to Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700; Normal-decreased CD4 numbers; T cell dysregulation; Low-normal B cells; Reduced IgG and IgA; Recurrent infections; chronic diarrhoea; inflammatory bowel disease; hypogammaglobulinaemia; pneumonitis; autoimmune disorders; thrombocytopaenia
Mendeliome v0.8640 LRBA Zornitza Stark Publications for gene: LRBA were set to
Mendeliome v0.8639 LRBA Zornitza Stark Mode of inheritance for gene: LRBA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 LRBA Zornitza Stark reviewed gene: LRBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22608502, 22721650, 25468195, 26206937, 33155142; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM# 614700, Normal-decreased CD4 numbers, T cell dysregulation, Low-normal B cells, Reduced IgG and IgA, Recurrent infections, chronic diarrhoea, inflammatory bowel disease, hypogammaglobulinaemia, pneumonitis, autoimmune disorders, thrombocytopaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8638 NFKBIA Danielle Ariti reviewed gene: NFKBIA: 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: 28597146, 23864385, 23708964; Phenotypes: Ectodermal dysplasia and immunodeficiency 2 MIM# 612132, Ectodermal dysplasia, TCR/ BCR activation impaired, low memory and isotype switched B cells, decreased IgG and IgA, elevated IgM, poor specific antibody responses, diarrhoea, agammaglobulinaemia, ectodermal dysplasia, recurrent respiratory and gastrointestinal infections, colitis, variable defects of skin, hair and teeth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB2 Danielle Ariti reviewed gene: NFKB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24140114, 24888602, 25524009, 31417880; Phenotypes: Immunodeficiency, common variable, 10 MIM# 615577, Low serum IgG, IgA, IgM, low B cell numbers, low switched memory B cells, Recurrent sinopulmonary infections, Alopecia, endocrinopathies, ACTH deficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 NFKB1 Danielle Ariti reviewed gene: NFKB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26279205, 32278790, 27022143, 7834752; Phenotypes: Immunodeficiency, common variable, 12 MIM# 616576, Normal-low IgG, IgA, IgM, low-normal B cells, low switched memory B cells, hypogammaglobulinaemia, recurrent respiratory and gastrointestinal infections, Chronic obstructive pulmonary disease COPD, EBV proliferation, autoimmunity, alopecia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8638 AQP2 Zornitza Stark Gene: aqp2 has been classified as Green List (High Evidence).
Mendeliome v0.8638 AQP2 Zornitza Stark Phenotypes for gene: AQP2 were changed from to Diabetes insipidus, nephrogenic, MIM#125800
Mendeliome v0.8637 AQP2 Zornitza Stark Publications for gene: AQP2 were set to
Mendeliome v0.8636 AQP2 Zornitza Stark Mode of inheritance for gene: AQP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8635 AQP2 Zornitza Stark reviewed gene: AQP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7537761, 11536078; Phenotypes: Diabetes insipidus, nephrogenic, MIM#125800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8635 RNF2 Zornitza Stark Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Lou-Schoch-Yamamoto syndrome , MIM#619460; epilepsy; intellectual disability; intrauterine growth retardation
Mendeliome v0.8634 RNF2 Zornitza Stark reviewed gene: RNF2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lou-Schoch-Yamamoto syndrome , MIM#619460; Mode of inheritance: None
Mendeliome v0.8634 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from Hao-Fountain syndrome, MIM# 616863; Intellectual disability; Autism to Hao-Fountain syndrome, MIM# 616863; MONDO:0014805; Intellectual disability; Autism
Mendeliome v0.8633 USP7 Zornitza Stark edited their review of gene: USP7: Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, MONDO:0014805, Intellectual disability, Autism
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8633 GIMAP5 Zornitza Stark Classified gene: GIMAP5 as Green List (high evidence)
Mendeliome v0.8633 GIMAP5 Zornitza Stark Gene: gimap5 has been classified as Green List (High Evidence).
Mendeliome v0.8632 GIMAP5 Zornitza Stark gene: GIMAP5 was added
gene: GIMAP5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP5 were set to 33956074
Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463
Review for gene: GIMAP5 was set to GREEN
Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration.
Sources: Expert list
Mendeliome v0.8631 ERBB2 Zornitza Stark Phenotypes for gene: ERBB2 were changed from to Visceral neuropathy, familial, 2, autosomal recessive, MIM# 619465
Mendeliome v0.8630 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy to Lethal congenital contractural syndrome 2, MIM# 607598; Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8629 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Visceral neuropathy, familial, 1, autosomal recessive, MIM# 243180, Complex neurocristinopathy
Mendeliome v0.8629 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Mendeliome v0.8629 IL7R Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers.
Mendeliome v0.8628 IL7R Zornitza Stark Publications for gene: IL7R were set to
Mendeliome v0.8627 IL7R Zornitza Stark Mode of inheritance for gene: IL7R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8626 MALT1 Zornitza Stark Marked gene: MALT1 as ready
Mendeliome v0.8626 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Mendeliome v0.8626 MALT1 Zornitza Stark Phenotypes for gene: MALT1 were changed from to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive
Mendeliome v0.8625 MALT1 Zornitza Stark Publications for gene: MALT1 were set to
Mendeliome v0.8624 MALT1 Zornitza Stark Mode of inheritance for gene: MALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8623 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Mendeliome v0.8623 IL2RG Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia
Mendeliome v0.8622 IL2RG Zornitza Stark Publications for gene: IL2RG were set to
Mendeliome v0.8621 IL2RG Zornitza Stark Mode of inheritance for gene: IL2RG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IL2RG Zornitza Stark reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8620 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Mendeliome v0.8620 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset
Mendeliome v0.8619 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to
Mendeliome v0.8618 IKZF1 Zornitza Stark Mode of inheritance for gene: IKZF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8617 IKZF1 Zornitza Stark reviewed gene: IKZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317; Phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8617 ITK Zornitza Stark Marked gene: ITK as ready
Mendeliome v0.8617 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Mendeliome v0.8617 ITK Zornitza Stark Phenotypes for gene: ITK were changed from to Lymphoproliferative syndrome 1 MIM# 613011; Lymphadenopathy; Recurrent infections; Hypogammaglobulinaemia; Evidence of EBV infection; EBV associated B cell Lymphoproliferation; High EBV viral load; Normal-low serum Ig; Depleted CD4+ T cells; Anaemia; Thrombocytopaenia; Hepatosplenomegaly
Mendeliome v0.8616 ITK Zornitza Stark Publications for gene: ITK were set to
Mendeliome v0.8615 ITK Zornitza Stark Mode of inheritance for gene: ITK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 MALT1 Danielle Ariti Deleted their comment
Mendeliome v0.8614 MALT1 Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN
Mendeliome v0.8614 IL7R Danielle Ariti reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843216, 19890784, 26123418, 11023514, 7964471; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971, fever, rash, failure to thrive, recurrent respiratory and gastric infections, diarrhoea, lymphadenopathy, pneumonitis, Pancytopaenia, low T-cell numbers, decreased immunoglobulins, normal-high B/NK-cell numbers.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 ITK Danielle Ariti reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011, Lymphadenopathy, Recurrent infections, Hypogammaglobulinaemia, Evidence of EBV infection, EBV associated B cell Lymphoproliferation, High EBV viral load, Normal-low serum Ig, Depleted CD4+ T cells, Anaemia, Thrombocytopaenia, Hepatosplenomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 MALT1 Danielle Ariti reviewed gene: MALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM# 615468, poor T-cell proliferation, normal T/B cell numbers, poor specific antibody response, recurrent bacterial/fungal/viral infections, bronchiectasis, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8614 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8614 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from to Auriculocondylar syndrome 2, MIM# 614669
Mendeliome v0.8613 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Mendeliome v0.8612 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PLCB4 Zornitza Stark reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8611 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Mendeliome v0.8611 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641
Mendeliome v0.8610 PBX1 Zornitza Stark Publications for gene: PBX1 were set to
Mendeliome v0.8609 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8608 PBX1 Zornitza Stark reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MIM# 617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8608 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from Pontocerebellar hypoplasia type 1A, MIM# 607596; SMA to Pontocerebellar hypoplasia type 1A, MIM# 607596; Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Mendeliome v0.8607 VRK1 Zornitza Stark Publications for gene: VRK1 were set to 19646678; 21937992; 25609612; 24126608; 27281532
Mendeliome v0.8606 VRK1 Zornitza Stark changed review comment from: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.; to: Complex phenotype with mixed peripheral and central neurological features. Two families reported where PCH was prominent and accompanied by ataxia. At least three families also reported where peripheral neuropathy dominated the clinical picture without PCH/ataxia.

Further delineation of phenotype 2021:
PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy. No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly. Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H.
Mendeliome v0.8606 VRK1 Zornitza Stark edited their review of gene: VRK1: Changed publications: 19646678, 21937992, 25609612, 24126608, 27281532, 34169149, 26583493; Changed phenotypes: Pontocerebellar hypoplasia type 1A, MIM# 607596, Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia
Mendeliome v0.8606 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Mendeliome v0.8606 CLCN3 Zornitza Stark Mode of inheritance for gene: CLCN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8605 CLCN3 Zornitza Stark Classified gene: CLCN3 as Green List (high evidence)
Mendeliome v0.8605 CLCN3 Zornitza Stark Gene: clcn3 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Marked gene: TNPO2 as ready
Mendeliome v0.8604 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8604 TNPO2 Zornitza Stark Phenotypes for gene: TNPO2 were changed from Developmental delays, neurologic deficits and dysmorphic features to Intellectual disability, neurologic deficits and dysmorphic features
Mendeliome v0.8603 TNPO2 Zornitza Stark Classified gene: TNPO2 as Green List (high evidence)
Mendeliome v0.8603 TNPO2 Zornitza Stark Gene: tnpo2 has been classified as Green List (High Evidence).
Mendeliome v0.8602 ZDHHC15 Daniel Flanagan reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: cerebral palsy, intellectual disability, autism spectrum disorder, epilepsy; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Mendeliome v0.8602 DNAH10 Zornitza Stark Classified gene: DNAH10 as Green List (high evidence)
Mendeliome v0.8602 DNAH10 Zornitza Stark Gene: dnah10 has been classified as Green List (High Evidence).
Mendeliome v0.8601 CLCN3 Kristin Rigbye gene: CLCN3 was added
gene: CLCN3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLCN3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN3 were set to PMID: 34186028
Phenotypes for gene: CLCN3 were set to Neurodevelopmental disorder
Mode of pathogenicity for gene: CLCN3 was set to Other
Review for gene: CLCN3 was set to GREEN
Added comment: 11 individuals reported, 9 that carried 8 different rare heterozygous missense variants in CLCN3, and 2 siblings that were homozygous for an NMD-predicted frameshift variant likely abolishing ClC-3 function. All missense variants were confirmed to be de novo in eight individuals for whom parental data was available.

The 11 individuals in the cohort share clinical features of variable severity. All 11 have GDD or ID and dysmorphic features, and a majority has mood or behavioural disorders and structural brain abnormalities:
- Structural brain abnormalities on MRI (9/11) included partial or full agenesis of the corpus callosum (6/9), disorganized cerebellar folia (4/9), delayed myelination (3/9), decreased white matter volume (3/9), pons hypoplasia (3/9), and dysmorphic dentate nuclei (3/9). Six of those with brain abnormalities also presented with seizures.
- Nine have abnormal vision, including strabismus in four and inability to fix or follow in the two with homozygous loss-of-function variants.
- Hypotonia ranging from mild to severe was reported in 7 of the 11 individuals.
- Six have mood or behavioural disorders, particularly anxiety (3/6).
- Consistent dysmorphic facial features included microcephaly, prominent forehead, hypertelorism, down-slanting palpebral fissures, full cheeks, and micrognathia.

The severity of disease in the two siblings with homozygous disruption of ClC-3 is consistent with the drastic phenotype seen in Clcn3 KO mice. The disease was more severe in two siblings carrying homozygous loss-of-function variants with the presence of GDD, absent speech, seizures, and salt and pepper fundal pigmentation in both individuals, with one deceased at 14 months of age. The siblings also had significant neuroanatomical findings including diffusely decreased white matter volume, thin corpora callosa, small hippocampi, and disorganized cerebellar folia. Supporting biallelic inheritance for LoF variants, disruption of mouse Clcn3 results in drastic neurodegeneration with loss of the hippocampus a few months after birth and early retinal degeneration. Clcn3−/− mice display severe neurodegeneration, whereas heterozygous Clcn3+/− mice appear normal.

Patch-clamp studies were used to investigate four of the missense variants. These suggested a gain of function in two variants with increased current in HEK cells, however they also showed reduced rectification of voltage and a loss of transient current, plus decreased current amplitude, glycosylation and surface expression when expressed in oocytes, and were suspected to interfere with channel gating and a negative feedback mechanism. These effects were also shown to vary depending on pH levels. The current of the remaining two variants did not differ from WT. For heterozygous missense variants, the disruption induced may be at least partially conferred to mutant/WT homodimers and mutant/ClC-4 heterodimers.

Both loss and gain of function in this gene resulted in the same phenotype.
Sources: Literature
Mendeliome v0.8601 TNPO2 Elena Savva gene: TNPO2 was added
gene: TNPO2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TNPO2 were set to PMID: 34314705
Phenotypes for gene: TNPO2 were set to Developmental delays, neurologic deficits and dysmorphic features
Mode of pathogenicity for gene: TNPO2 was set to Other
Review for gene: TNPO2 was set to GREEN
Added comment: PMID: 34314705 - all de novo missense variants with intellectual disability (9/9), speech impairment (15/15), motor impairment (15/15), ophthalmologic abnormalities (10/15), muscle tone abnormalities (11/15, primarily hypotonia), seizures (6/15, febrile to non-febrile), microcephaly (5/15) and MRI anomalies (7/13, 3/13 had cerebellar hypoplasia/dysplasia).

Null fly model was homozygous lethal, no obvious phenotypes in heterozygotes. Upregulated gene expression also resulted in lethality. Overexpression of some human variants in fly models resulted in "toxicity" and phenotypic defects, authors speculate two variants are GOF, 1 variant is LOF.

gnomAD: minimal PTCs present
Sources: Literature
Mendeliome v0.8601 SPTBN4 Melanie Marty Deleted their review
Mendeliome v0.8601 DNAH10 Ain Roesley gene: DNAH10 was added
gene: DNAH10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAH10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH10 were set to 34237282
Phenotypes for gene: DNAH10 were set to primary male infertility with asthenoteratozoospermia
Penetrance for gene: DNAH10 were set to unknown
Review for gene: DNAH10 was set to GREEN
Added comment: 4x families with 5 affecteds (chets and homs - 4 missense and 2 fs). Knockout mouse models were infertile and showed significant reduction in count and motility compared to heterozygous mice
Sources: Literature
Mendeliome v0.8601 AP1G1 Zornitza Stark Added comment: Comment when marking as ready: Good evidence for association between mono-allelic variants and NDD, moderate evidence for bi-allelic variants causing disease.
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8601 ALDH1A2 Seb Lunke commented on gene: ALDH1A2
Mendeliome v0.8601 AP1G1 Zornitza Stark Classified gene: AP1G1 as Green List (high evidence)
Mendeliome v0.8601 AP1G1 Zornitza Stark Gene: ap1g1 has been classified as Green List (High Evidence).
Mendeliome v0.8600 SEMA3D Ain Roesley edited their review of gene: SEMA3D: Added comment: Reported as a common susceptibility loci. No reported evidence for an association with Mendelian disease. Sema3d null heterozygote and homozygote mouse model had normal intestinal innervation.; Changed publications: 28334784, 25839327; Changed phenotypes: Hirschsprung disease
Mendeliome v0.8600 AP1G1 Danielle Ariti gene: AP1G1 was added
gene: AP1G1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AP1G1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AP1G1 were set to 34102099
Phenotypes for gene: AP1G1 were set to Neurodevelopmental disorder (NDD); Intellectual Disability; Epilepsy
Mode of pathogenicity for gene: AP1G1 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: AP1G1 was set to GREEN
Added comment: Two bi-allelic homozygous missense variants were found in two distinct families with Italian and Pakistani origins; homozygous missense variants.

Eight de novo heterozygous variants were identified in nine isolated affected individuals from nine families; including five missense, two frameshift, and one intronic variant that disrupts the canonical splice acceptor site.

Knocking out AP1G1 Zebrafish model resulted in severe developmental abnormalities and increased lethality.

All individuals had neurodevelopmental disorder (NDD) including global developmental delay and ID, which varied in severity from mild to severe.
Sources: Literature
Mendeliome v0.8600 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Mendeliome v0.8600 SEMA3D Zornitza Stark Phenotypes for gene: SEMA3D were changed from to Hand and foot malformations
Mendeliome v0.8599 SEMA3D Zornitza Stark Classified gene: SEMA3D as Red List (low evidence)
Mendeliome v0.8599 SEMA3D Zornitza Stark Gene: sema3d has been classified as Red List (Low Evidence).
Mendeliome v0.8598 SPTBN1 Belinda Chong changed review comment from: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature; to: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures (9/29); behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8598 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Mendeliome v0.8598 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Mendeliome v0.8598 SPTBN4 Zornitza Stark Phenotypes for gene: SPTBN4 were changed from to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519)
Mendeliome v0.8597 TP73 Seb Lunke Classified gene: TP73 as Green List (high evidence)
Mendeliome v0.8597 TP73 Seb Lunke Gene: tp73 has been classified as Green List (High Evidence).
Mendeliome v0.8597 SPTBN4 Zornitza Stark Publications for gene: SPTBN4 were set to
Mendeliome v0.8596 SPTBN4 Zornitza Stark Mode of inheritance for gene: SPTBN4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8595 TP73 Seb Lunke Publications for gene: TP73 were set to PMID: 31130284
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Mendeliome v0.8594 HMGB1 Zornitza Stark Classified gene: HMGB1 as Red List (low evidence)
Mendeliome v0.8594 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Red List (Low Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Marked gene: SPTBN1 as ready
Mendeliome v0.8593 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8593 SPTBN1 Zornitza Stark Phenotypes for gene: SPTBN1 were changed from Neurodevelopmental Syndrome to Neurodevelopmental Syndrome; Intellectual disability; Seizures
Mendeliome v0.8592 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8592 EDEM3 Seb Lunke Phenotypes for gene: EDEM3 were changed from EDEM3-congenital disorder of glycosylation to Congenital disorder of glycosylation; Developmental delay
Mendeliome v0.8591 UBA2 Ain Roesley changed review comment from: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation. Her daughter and grandson reported to have ectrofactyly but were unavailable for testing; to: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing
Mendeliome v0.8591 SPTBN1 Zornitza Stark Classified gene: SPTBN1 as Green List (high evidence)
Mendeliome v0.8591 SPTBN1 Zornitza Stark Gene: sptbn1 has been classified as Green List (High Evidence).
Mendeliome v0.8590 EDEM3 Seb Lunke Classified gene: EDEM3 as Green List (high evidence)
Mendeliome v0.8590 EDEM3 Seb Lunke Gene: edem3 has been classified as Green List (High Evidence).
Mendeliome v0.8589 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Mendeliome v0.8588 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Mendeliome v0.8588 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Mendeliome v0.8587 ALDH1A2 Ain Roesley reviewed gene: ALDH1A2: Rating: RED; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8587 GCNA Zornitza Stark Classified gene: GCNA as Green List (high evidence)
Mendeliome v0.8587 GCNA Zornitza Stark Gene: gcna has been classified as Green List (High Evidence).
Mendeliome v0.8586 SEMA3D Ain Roesley gene: SEMA3D was added
gene: SEMA3D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEMA3D were set to 34159400
Penetrance for gene: SEMA3D were set to unknown
Review for gene: SEMA3D was set to RED
Added comment: 1x de novo missense in a proband with short stature, absent distal phalanges of the 5th fingers and toes, and dysplastic middle phalanges of the toes.

However, there is 4 hets in gnomAD v2
Sources: Literature
Mendeliome v0.8586 SPTBN4 Melanie Marty reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33772159; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8586 TP73 Ee Ming Wong changed review comment from: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- Epithelial cells from TP73 variant carriers showed reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls; to: - Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants)
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls
Mendeliome v0.8586 TP73 Ee Ming Wong reviewed gene: TP73: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34077761; Phenotypes: chronic airway disease, brain malformation, lissencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8586 HMGB1 Ain Roesley changed review comment from: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature; to: 1x de novo fs in a proband with severe mirror image foot polydactyly. No functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 HMGB1 Ain Roesley gene: HMGB1 was added
gene: HMGB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HMGB1 were set to 34159400
Phenotypes for gene: HMGB1 were set to Mirror image foot polydactyly
Penetrance for gene: HMGB1 were set to unknown
Review for gene: HMGB1 was set to RED
Added comment: 1x de novo fs, no functional studies done but cited Itou 2011 - mouse and zebrafish studies demonstrated the role of HMGB1 in regulating digit number during embryonic limb development
Sources: Literature
Mendeliome v0.8586 SPTBN1 Belinda Chong gene: SPTBN1 was added
gene: SPTBN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTBN1 were set to PMID: 34211179; PMID: 33847457
Phenotypes for gene: SPTBN1 were set to Neurodevelopmental Syndrome
Review for gene: SPTBN1 was set to GREEN
Added comment: PMID: 34211179
- Heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features.
- Show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics.

PMID: 33847457
- Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset.
- identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities).
- Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis.
Sources: Literature
Mendeliome v0.8586 UBA2 Ain Roesley reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34159400; Phenotypes: isolated split hand malformation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8586 EDEM3 Michelle Torres gene: EDEM3 was added
gene: EDEM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to EDEM3-congenital disorder of glycosylation
Review for gene: EDEM3 was set to GREEN
Added comment: PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional show LoF of EDEM3 enzymatic activity.
Sources: Literature
Mendeliome v0.8586 GCNA Ain Roesley gene: GCNA was added
gene: GCNA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GCNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GCNA were set to 33963445
Phenotypes for gene: GCNA were set to primary spermatogenic failure
Penetrance for gene: GCNA were set to unknown
Review for gene: GCNA was set to GREEN
Added comment: 7x probands all missense except 1 fs. Variants had <0.0005 MAF in gnomad v2 male cohort and absent in 5784 Dutch control cohort
no functional studies were done except for histology of Ser659Trp, revealing a Sertoli-cell only
Sources: Literature
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8586 ANK2 Zornitza Stark Classified gene: ANK2 as Green List (high evidence)
Mendeliome v0.8586 ANK2 Zornitza Stark Gene: ank2 has been classified as Green List (High Evidence).
Mendeliome v0.8585 ANK2 Zornitza Stark gene: ANK2 was added
gene: ANK2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 31983240; 22542183; 25363768; 27479843; 28554332; 30564305; 30755392; 31981491; 33004838; 33057194
Phenotypes for gene: ANK2 were set to Long QT syndrome 4, MIM# 600919; Complex neurodevelopmental disorder, MONDO:0100038
Review for gene: ANK2 was set to GREEN
Added comment: Link with cardiac abnormalities such as LongQT is DISPUTED. More than 10 unrelated individuals reported with neurodevelopmental phenotype, comprising autism/ID and de novo truncating variants, in addition to many other individuals as part of large NDD cohorts. This association has been assessed as DEFINITIVE by ClinGen.
Sources: Expert Review
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8584 PRDX3 Zornitza Stark Classified gene: PRDX3 as Green List (high evidence)
Mendeliome v0.8584 PRDX3 Zornitza Stark Gene: prdx3 has been classified as Green List (High Evidence).
Mendeliome v0.8583 PRDX3 Hazel Phillimore changed review comment from: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature; to: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mendeliome v0.8583 PRDX3 Hazel Phillimore gene: PRDX3 was added
gene: PRDX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDX3 were set to PMID: 33889951
Phenotypes for gene: PRDX3 were set to cerebellar ataxia (early onset, mild to moderate, progressive)
Penetrance for gene: PRDX3 were set to unknown
Review for gene: PRDX3 was set to GREEN
Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex.
Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres.
The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote of a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism.
The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense.
Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity.
PRXD3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated.
Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species.
In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress.
Sources: Literature
Mendeliome v0.8583 GSC Zornitza Stark Gene: gsc has been classified as Green List (High Evidence).
Mendeliome v0.8583 GSC Zornitza Stark Phenotypes for gene: GSC were changed from to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471
Mendeliome v0.8582 GSC Zornitza Stark Publications for gene: GSC were set to
Mendeliome v0.8581 GSC Zornitza Stark Mode of inheritance for gene: GSC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GSC Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8580 GNAI3 Zornitza Stark Gene: gnai3 has been classified as Green List (High Evidence).
Mendeliome v0.8580 GNAI3 Zornitza Stark Phenotypes for gene: GNAI3 were changed from to Auriculocondylar syndrome 1, OMIM #602483
Mendeliome v0.8579 GNAI3 Zornitza Stark Publications for gene: GNAI3 were set to
Mendeliome v0.8578 GNAI3 Zornitza Stark Mode of inheritance for gene: GNAI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8577 GNAI3 Zornitza Stark reviewed gene: GNAI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091; Phenotypes: Auriculocondylar syndrome 1, OMIM #602483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8577 EIF4A3 Zornitza Stark Gene: eif4a3 has been classified as Green List (High Evidence).
Mendeliome v0.8577 EIF4A3 Zornitza Stark Phenotypes for gene: EIF4A3 were changed from to Robin sequence with cleft mandible and limb anomalies, MIM# 268305; Richieri-Costa-Pereira syndrome
Mendeliome v0.8576 EIF4A3 Zornitza Stark Publications for gene: EIF4A3 were set to
Mendeliome v0.8575 EIF4A3 Zornitza Stark Mode of inheritance for gene: EIF4A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8574 EIF4A3 Zornitza Stark reviewed gene: EIF4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24360810; Phenotypes: Robin sequence with cleft mandible and limb anomalies, MIM# 268305, Richieri-Costa-Pereira syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Changed phenotypes: Complex neurocristinopathy
Mendeliome v0.8574 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Complex neurocristinopathy
Mendeliome v0.8573 ERBB3 Zornitza Stark changed review comment from: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; to: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease.
Mendeliome v0.8573 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis; Neurodevelopmental disorder with gut dysmotility
Mendeliome v0.8572 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 17701904; 31752936; 33720042
Mendeliome v0.8571 ERBB3 Zornitza Stark changed review comment from: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.; to: Lethal congenital contractual syndrome: Two families reported with contractures, positional approach used in gene discovery (2007). Another family reported more recently with a multi-system disorder but without contractures.
Mendeliome v0.8571 ERBB3 Zornitza Stark edited their review of gene: ERBB3: Added comment: PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and neurodevelopmental disorder. Note variants in this gene have also recently been linked to Hirschsprung's disease.; Changed rating: GREEN; Changed publications: 17701904, 31752936, 33497358; Changed phenotypes: Lethal congenital contractural syndrome 2, MIM# 607598, Neurodevelopmental disorder with gut dysmotility
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8571 PDCL3 Zornitza Stark Classified gene: PDCL3 as Amber List (moderate evidence)
Mendeliome v0.8571 PDCL3 Zornitza Stark Gene: pdcl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8570 PDCL3 Zornitza Stark gene: PDCL3 was added
gene: PDCL3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PDCL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCL3 were set to 32621347
Phenotypes for gene: PDCL3 were set to Megacystis-microcolon
Review for gene: PDCL3 was set to AMBER
Added comment: Single publication (PMID 32621347): one family with two affected fetuses - one with megacystis and microcolon, and the other with megacystisis and bilateral diaphragmatic hernia (prune-belly phenotype). Compound het LOF variants in PDCL3 (one frameshift and one missense). Complete absence of PDLC3 expression demonstrated in one of the affected fetuses. No homozygous LOF PDCL3 variants in gnomAD. PCDL3 negatively modulates actin folding and is strongly expressed in smooth muscle of bladder and colon.
Sources: Expert Review
Mendeliome v0.8569 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8569 SGO1 Zornitza Stark Phenotypes for gene: SGO1 were changed from to Chronic atrial and intestinal dysrhythmia, MIM# 616201
Mendeliome v0.8568 SGO1 Zornitza Stark Publications for gene: SGO1 were set to
Mendeliome v0.8567 SGO1 Zornitza Stark Mode of inheritance for gene: SGO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8566 SGO1 Zornitza Stark Classified gene: SGO1 as Amber List (moderate evidence)
Mendeliome v0.8566 SGO1 Zornitza Stark Gene: sgo1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8565 SGO1 Zornitza Stark reviewed gene: SGO1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8565 TYMP Zornitza Stark Marked gene: TYMP as ready
Mendeliome v0.8565 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Mendeliome v0.8565 TYMP Zornitza Stark Phenotypes for gene: TYMP were changed from to Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041; MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy
Mendeliome v0.8564 TYMP Zornitza Stark Publications for gene: TYMP were set to
Mendeliome v0.8563 TYMP Zornitza Stark Mode of inheritance for gene: TYMP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9924029, 14757860; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), MIM# 603041, MNGIE: ptosis, ophthalmoplegia & ophthalmoparesis, hearing loss, neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8562 ZNF687 Zornitza Stark Gene: znf687 has been classified as Green List (High Evidence).
Mendeliome v0.8562 ZNF687 Zornitza Stark Phenotypes for gene: ZNF687 were changed from to Paget disease of bone 6, MIM#616833
Mendeliome v0.8561 ZNF687 Zornitza Stark Publications for gene: ZNF687 were set to
Mendeliome v0.8560 ZNF687 Zornitza Stark Mode of inheritance for gene: ZNF687 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 ZNF687 Zornitza Stark Tag founder tag was added to gene: ZNF687.
Mendeliome v0.8559 ZNF687 Zornitza Stark reviewed gene: ZNF687: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8559 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Mendeliome v0.8559 GRHPR Zornitza Stark Phenotypes for gene: GRHPR were changed from to Hyperoxaluria, primary, type II, MIM# 260000; MONDO:0009824
Mendeliome v0.8558 GRHPR Zornitza Stark Publications for gene: GRHPR were set to
Mendeliome v0.8557 GRHPR Zornitza Stark Mode of inheritance for gene: GRHPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 GRHPR Zornitza Stark reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10484776, 11030416, 24116921; Phenotypes: Hyperoxaluria, primary, type II, MIM# 260000, MONDO:0009824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8556 AGXT Zornitza Stark Marked gene: AGXT as ready
Mendeliome v0.8556 AGXT Zornitza Stark Gene: agxt has been classified as Green List (High Evidence).
Mendeliome v0.8556 AGXT Zornitza Stark Phenotypes for gene: AGXT were changed from to Hyperoxaluria, primary, type 1, MIM# 259900; MONDO:0009823
Mendeliome v0.8555 AGXT Zornitza Stark Publications for gene: AGXT were set to
Mendeliome v0.8554 AGXT Zornitza Stark Mode of inheritance for gene: AGXT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 AGXT Zornitza Stark reviewed gene: AGXT: Rating: GREEN; Mode of pathogenicity: None; Publications: 2039493, 19479957; Phenotypes: Hyperoxaluria, primary, type 1, MIM# 259900, MONDO:0009823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8553 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Mendeliome v0.8553 HOGA1 Zornitza Stark Phenotypes for gene: HOGA1 were changed from to Hyperoxaluria, primary, type III MIM#613616
Mendeliome v0.8552 HOGA1 Zornitza Stark Publications for gene: HOGA1 were set to
Mendeliome v0.8551 HOGA1 Zornitza Stark Mode of inheritance for gene: HOGA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8550 ZNF687 Ain Roesley reviewed gene: ZNF687: Rating: AMBER; Mode of pathogenicity: None; Publications: 26849110, 29493781, 32106343; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8550 HOGA1 Paul De Fazio reviewed gene: HOGA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20797690, 21896830, 22391140; Phenotypes: Hyperoxaluria, primary, type III MIM#613616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8550 VPS45 Zornitza Stark Gene: vps45 has been classified as Green List (High Evidence).
Mendeliome v0.8550 VPS45 Zornitza Stark Phenotypes for gene: VPS45 were changed from to Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285
Mendeliome v0.8549 VPS45 Zornitza Stark Publications for gene: VPS45 were set to
Mendeliome v0.8548 VPS45 Zornitza Stark Mode of inheritance for gene: VPS45 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 VPS45 Zornitza Stark reviewed gene: VPS45: Rating: GREEN; Mode of pathogenicity: None; Publications: 23738510, 23599270, 33623350, 32037586, 30294941; Phenotypes: Neutropaenia, severe congenital, 5, autosomal recessive, MIM# 615285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Marked gene: LAMTOR2 as ready
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8547 LAMTOR2 Zornitza Stark Phenotypes for gene: LAMTOR2 were changed from to Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798
Mendeliome v0.8546 LAMTOR2 Zornitza Stark Publications for gene: LAMTOR2 were set to
Mendeliome v0.8545 LAMTOR2 Zornitza Stark Mode of inheritance for gene: LAMTOR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Classified gene: LAMTOR2 as Amber List (moderate evidence)
Mendeliome v0.8544 LAMTOR2 Zornitza Stark Gene: lamtor2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 LAMTOR2 Zornitza Stark reviewed gene: LAMTOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 17195838, 24092934; Phenotypes: Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8543 IKZF3 Zornitza Stark Classified gene: IKZF3 as Amber List (moderate evidence)
Mendeliome v0.8543 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8542 IKZF3 Zornitza Stark gene: IKZF3 was added
gene: IKZF3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF3 were set to 34155405
Phenotypes for gene: IKZF3 were set to Immunodeficiency 84, MIM# 619437
Review for gene: IKZF3 was set to AMBER
Added comment: Single family reported where heterozygous missense variant in this gene segregated with immunodeficiency in a mother and two children. Findings included low levels of B cells and impaired early B-cell development, variable T-cell abnormalities, hypogammaglobulinaemia, increased susceptibility to infection with Epstein-Barr virus (EBV). One individual developed lymphoma in adulthood. Mouse model recapitulated phenotype.
Sources: Expert Review
Mendeliome v0.8541 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Mendeliome v0.8541 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to D-bifunctional protein deficiency, AR (MIM#261515); Perrault syndrome 1, AR (MIM#233400)
Mendeliome v0.8540 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Mendeliome v0.8539 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 HSD17B4 Michelle Torres reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27790638; Phenotypes: D-bifunctional protein deficiency, AR (MIM#261515), Perrault syndrome 1, AR (MIM#233400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8538 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8538 LCK Zornitza Stark Phenotypes for gene: LCK were changed from to Immunodeficiency 22 MIM# 615758; Recurrent infections; Immune dysregulation; autoimmunity; Low CD4+; low CD8+; restricted T cell repertoire; poor TCR signaling; Normal IgG/IgA; high IgM; failure to thrive; diarrhoea; lymphopaenia; hypogammaglobulinaemia; anaemia; thrombocytopaenia; CD4+ T-cell lymphopaenia
Mendeliome v0.8537 LCK Zornitza Stark Publications for gene: LCK were set to
Mendeliome v0.8536 LCK Zornitza Stark Mode of inheritance for gene: LCK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8535 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8535 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8534 LCK Zornitza Stark Classified gene: LCK as Amber List (moderate evidence)
Mendeliome v0.8534 LCK Zornitza Stark Gene: lck has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8533 LCK Zornitza Stark reviewed gene: LCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 22985903, 1579166, 11021796; Phenotypes: Immunodeficiency 22 MIM# 615758, Recurrent infections, Immune dysregulation, autoimmunity, Low CD4+, low CD8+, restricted T cell repertoire, poor TCR signaling, Normal IgG/IgA, high IgM, failure to thrive, diarrhoea, lymphopenia, hypogammaglobulinemia, anaemia, thrombocytopaenia, CD4+ T-cell lymphopenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8533 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Mendeliome v0.8533 DOCK8 Zornitza Stark Phenotypes for gene: DOCK8 were changed from to Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700; T cell Lymphopaenia; decraese T/B/NK cells; Eosinophilia; low IgM; elevated IgE; recurrent cutaneous/ viral/ bacterial/ fungal/ infections; severe atopy/allergic disease; autoimmune haemolytic anaemia; eczema; cancer diathesis
Mendeliome v0.8532 DOCK8 Zornitza Stark Publications for gene: DOCK8 were set to
Mendeliome v0.8531 DOCK8 Zornitza Stark Mode of inheritance for gene: DOCK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8530 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Mendeliome v0.8530 DOCK2 Zornitza Stark Phenotypes for gene: DOCK2 were changed from to Immunodeficiency 40 MIM# 616433; T/B-cell lymphopaenia; early-onset invasive herpes/viral/bacterial Infections; function defects in T/B/NK cells; immunodeficiency; defective IFN-mediated immunity; elevated IgM; normal IgG/IgA levels
Mendeliome v0.8529 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Mendeliome v0.8528 DOCK2 Zornitza Stark Mode of inheritance for gene: DOCK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK2 Zornitza Stark reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364, 30838481, 11518968; Phenotypes: Immunodeficiency 40 MIM# 616433, T/B-cell lymphopaenia, early-onset invasive herpes/viral/bacterial Infections, function defects in T/B/NK cells, immunodeficiency, defective IFN-mediated immunity, elevated IgM, normal IgG/IgA levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DOCK8 Danielle Ariti reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700, T cell Lymphopaenia, decraese T/B/NK cells, Eosinophilia, low IgM, elevated IgE, recurrent cutaneous/ viral/ bacterial/ fungal/ infections, severe atopy/allergic disease, autoimmune haemolytic anaemia, eczema, cancer diathesisc; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8527 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Mendeliome v0.8527 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Mendeliome v0.8527 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells
Mendeliome v0.8526 DNMT3B Zornitza Stark Publications for gene: DNMT3B were set to
Mendeliome v0.8525 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 DNMT3B Zornitza Stark reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8524 TMPO Bryony Thompson Marked gene: TMPO as ready
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8524 TMPO Bryony Thompson Classified gene: TMPO as Red List (low evidence)
Mendeliome v0.8524 TMPO Bryony Thompson Gene: tmpo has been classified as Red List (Low Evidence).
Mendeliome v0.8523 TMPO Bryony Thompson reviewed gene: TMPO: Rating: RED; Mode of pathogenicity: None; Publications: 16247757; Phenotypes: Hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8523 SYNCRIP Zornitza Stark Classified gene: SYNCRIP as Green List (high evidence)
Mendeliome v0.8523 SYNCRIP Zornitza Stark Gene: syncrip has been classified as Green List (High Evidence).
Mendeliome v0.8522 SYNCRIP Zornitza Stark gene: SYNCRIP was added
gene: SYNCRIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937
Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology
Review for gene: SYNCRIP was set to GREEN
Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases.

Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals.

The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence.

Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance.

Overall the variants reported to date include [NM_006372.5]:
1 - c.858_859del p.(Gly287Leufs*5)
2 - c.854dupA p.(Asn285Lysfs*8)
3 - c.734T>C p.(Leu245Pro)
4 - chr6:85605276-85683190 deletion (GRCh38)
5 - c.629T>C p.(Phe210Ser)
6 - c.1573_1574delinsTT p.(Gln525Leu)
7 - c.1247_1250del p.(Arg416Lysfs*145)
8 - c.1518_1519insC p.(Ala507Argfs*14)

[P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1]

SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation.

Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD.

The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2.

There are no additional studies performed.

Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%]

Animal models are not discussed.

There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes.
Sources: Literature
Mendeliome v0.8521 MSN Zornitza Stark Gene: msn has been classified as Green List (High Evidence).
Mendeliome v0.8521 MSN Zornitza Stark Phenotypes for gene: MSN were changed from to Immunodeficiency 50, MIM# 300988
Mendeliome v0.8520 MSN Zornitza Stark Publications for gene: MSN were set to
Mendeliome v0.8519 MSN Zornitza Stark Mode of inheritance for gene: MSN was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8518 MSN Zornitza Stark reviewed gene: MSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27405666; Phenotypes: Immunodeficiency 50, MIM# 300988; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8518 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Mendeliome v0.8518 JAGN1 Zornitza Stark Phenotypes for gene: JAGN1 were changed from to Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022
Mendeliome v0.8517 JAGN1 Zornitza Stark Publications for gene: JAGN1 were set to
Mendeliome v0.8516 JAGN1 Zornitza Stark Mode of inheritance for gene: JAGN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 JAGN1 Zornitza Stark reviewed gene: JAGN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25129144; Phenotypes: Neutropaenia, severe congenital, 6, autosomal recessive, MIM# 616022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8515 ITGB2 Zornitza Stark Marked gene: ITGB2 as ready
Mendeliome v0.8515 ITGB2 Zornitza Stark Gene: itgb2 has been classified as Green List (High Evidence).
Mendeliome v0.8515 ITGB2 Zornitza Stark Phenotypes for gene: ITGB2 were changed from to Leukocyte adhesion deficiency, MIM# 116920
Mendeliome v0.8514 ITGB2 Zornitza Stark Publications for gene: ITGB2 were set to
Mendeliome v0.8513 ITGB2 Zornitza Stark Mode of inheritance for gene: ITGB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 ITGB2 Zornitza Stark reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911, 1694220, 33957747, 32279896, 31374327; Phenotypes: Leukocyte adhesion deficiency, MIM# 116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8512 NLRP2 Melanie Marty commented on gene: NLRP2
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8512 CAMK4 Zornitza Stark Classified gene: CAMK4 as Green List (high evidence)
Mendeliome v0.8512 CAMK4 Zornitza Stark Gene: camk4 has been classified as Green List (High Evidence).
Mendeliome v0.8511 CAMK4 Zornitza Stark gene: CAMK4 was added
gene: CAMK4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CAMK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK4 were set to 30262571; 33098801; 33211350
Phenotypes for gene: CAMK4 were set to Intellectual disability; Autism; Behavioral abnormality; Abnormality of movement; Dystonia; Ataxia; Chorea; Myoclonus
Review for gene: CAMK4 was set to GREEN
Added comment: 3 publications by Zech et al (2018, 2020 - PMIDs : 30262571, 33098801, 33211350) provide clinical details on 3 individuals, each harboring a private de novo CAMK4 variant.

Overlapping features included DD, ID, behavoral issues, autism and abnormal hyperkinetic movements. Dystonia and chorea in all 3 appeared 3-20 years after initial symptoms.

CAMK4 encodes Calcium/Calmodulin-dependent protein kinase IV, an important mediator of calcium-mediated activity and dynamics, particularly in the brain. It is involved in neuronal transmission, synaptic plasticity, and neuronal gene expression required for brain development and neuronal homeostasis (summary by OMIM based on Zech et al, 2018).

The 473 aa enzyme has a protein kinase domain (aa 46-300) and a C-terminal autoregulatory domain (aa 305-341) the latter comprising an autoinhibitory domain (AID / aa 305-321) and a calmodulin-binding domain (CBD / aa 322-341) [NP_001735.1 / NM_001744.4 - also used below].

Variants in all 3 subjects were identified following trio-WES and were in all cases protein-truncating, mapping to exon 10 or exon 10-intron 10 junction, expected to escape NMD and cause selective abrogation of the autoinhibitory domain (aa 305-321) leading overall to gain-of-function.

Variation databases include pLoF CAMK4 variants albeit in all cases usptream or downstream of this region (pLI of this gene in gnomAD: 0.51). Variants leading to selective abrogation of the autoregulatory domain have not been reported.

Extensive evidence for the GoF effect of the variant has been provided in the first publication. Several previous studies have demonstrated that abrogation of the AID domain leads to consitutive activation (details below).

Mouse models - though corresponding to homozygous loss of function - support a role for CAMKIV in cognitive and motor symptoms. Null mice display tremulous and ataxic movements, deficiencies in balance and sensorimotor performance associated with reduced number of Purkinje neurons (Ribar et al 2000, PMID: 11069976 - not reviewed). Wei et al (2002, PMID: 12006982 - not reviewed) provided evidence for alteration in hippocampal physiology and memory function.

Heterozygous mutations in other genes for calcium/calmodulin-dependent protein kinases (CAMKs) e.g. CAMK2A/CAMK2B (encoding subunits of CAMKII) have been reported in individuals with ID.

---

The proband in the first publication (PMID: 30262571) was a male with DD, ID, behavioral difficulties (ASD, autoaggression, stereotypies) and hyperkinetic movement disorder (myoclonus, chorea, ataxia) with severe generalized dystonia (onset at the age of 13y). Brain MRI demonstrated cerebellar atrophy.

Extensive work-up incl. karyotyping, CMA, DYT-TOR1A, THAP1, GCH1, SCA1/2/3/6/7/8/12/17, Friedreich's ataxia and FMR1 analysis was negative.F

Trio WES identified a dn splice site variant (c.981+1G>A) in the last exon-intron junction. RT-PCR followed by gel electrophoresis and Sanger in fibroblasts from an affected and control subject revealed that the proband had - as predicted by the type/location of the variant - in equal amount 2 cDNA products, a normal as well as a truncated one.

Sequencing of the shortest revealed utilization of a cryptic donor splice site upstream of the mutated donor leading to a 77bp out-of-frame deletion and introduction of a premature stop codon in the last codon (p.Lys303Serfs*28). Western blot in fibroblast cell lines revealed 2 bands corresponding to the normal protein product as well as to the p.Lys303Serfs*28 although expression of the latter was lower than that of the full length protein.

Several previous studies have shown that mutant CAMKIV species that lack the autoinhibitory domain are consitutively active (several Refs provided). Among others Chatila et al (1996, PMID: 8702940) studied an in vitro-engineered truncation mutant (Δ1-317 - truncation at position 317 of the protein) with functionally validated gain-of-function effect.

To prove enhanced activity of the splicing variant, Zech et al assessed phosphorylation of CREB (cyclic AMP-responsive element binding protein), a downstream substrate of CAMKIV. Immunobloting revealed significant increase of CREB phosphorylation in patient fibroblasts compared to controls. Overactivation of CAMKIV signaling was reversed when cells were treated with STO-609 an inhibitor of CAMKK, the ustream activator of CAMKIV.

Overall the authors demonstrated that loss of CAMKIV autoregulatory domain due to this splice variant had a gain-of-function effect.

----

Following trio-WES, Zech et al (2020 - PMID: 33098801) identified another relevant subject within cohort of 764 individuals with dystonia. This 12-y.o. male, harboring a different variant affecting the same donor site (c.981+1G>T), presented DD, ID, dystonia (onset at 3y) and additional movement disorders (myoclonus, ataxia) as well as similar behavior (ASD, autoaggression, stereotypies). [Details in suppl. p20].

----

Finally Zech et al (2020 - PMID: 33211350) reported on a 24-y.o. woman with adolescence onset choreodystonia. Other features included DD, moderate ID, absence seizures in infancy, OCD with anxiety and later diagnosis of ASD. Trio WES revealed a dn stopgain variant (c.940C>T; p.Gln314*).
Sources: Expert Review
Mendeliome v0.8510 FERMT3 Zornitza Stark Marked gene: FERMT3 as ready
Mendeliome v0.8510 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Green List (High Evidence).
Mendeliome v0.8510 FERMT3 Zornitza Stark Phenotypes for gene: FERMT3 were changed from to Leukocyte adhesion deficiency, type III, MIM# 612840
Mendeliome v0.8509 FERMT3 Zornitza Stark Publications for gene: FERMT3 were set to
Mendeliome v0.8508 FERMT3 Zornitza Stark Mode of inheritance for gene: FERMT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 FERMT3 Zornitza Stark reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234460, 19064721; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8507 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700 to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Neutropaenia, cyclic, MIM# 162800
Mendeliome v0.8506 ELANE Zornitza Stark edited their review of gene: ELANE: Changed phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700, Neutropaenia, cyclic, MIM# 162800
Mendeliome v0.8506 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Mendeliome v0.8506 CYBB Zornitza Stark Phenotypes for gene: CYBB were changed from to Chronic granulomatous disease, X-linked, MIM# 306400
Mendeliome v0.8505 CYBB Zornitza Stark Publications for gene: CYBB were set to
Mendeliome v0.8504 CYBB Zornitza Stark Mode of inheritance for gene: CYBB was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8503 CYBB Zornitza Stark reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: None; Publications: 2556453, 1710153, 9585602; Phenotypes: Chronic granulomatous disease, X-linked, MIM# 306400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8503 CSF3R Zornitza Stark Gene: csf3r has been classified as Green List (High Evidence).
Mendeliome v0.8503 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014 to Neutropaenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8502 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from to Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014
Mendeliome v0.8501 CSF3R Zornitza Stark Publications for gene: CSF3R were set to
Mendeliome v0.8500 CSF3R Zornitza Stark Mode of inheritance for gene: CSF3R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 CSF3R Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported. Some reports of progression to myelodysplasia.
Mendeliome v0.8499 CSF3R Zornitza Stark reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753537, 26324699, 33511998, 32966608; Phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8499 NUAK2 Zornitza Stark Phenotypes for gene: NUAK2 were changed from Anencephaly to Anencephaly 2, MIM# 619452
Mendeliome v0.8498 NUAK2 Zornitza Stark Deleted their comment
Mendeliome v0.8498 NUAK2 Zornitza Stark edited their review of gene: NUAK2: Changed phenotypes: Anencephaly 2, MIM# 619452
Mendeliome v0.8498 DBR1 Zornitza Stark Phenotypes for gene: DBR1 were changed from Viral infections of the brainstem to {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441; Viral infections of the brainstem
Mendeliome v0.8497 DBR1 Zornitza Stark edited their review of gene: DBR1: Changed phenotypes: {Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}, MIM# 619441, Viral infections of the brainstem
Mendeliome v0.8497 DPYSL5 Zornitza Stark Phenotypes for gene: DPYSL5 were changed from Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities to Ritscher-Schinzel syndrome 4, MIM# 619435; Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Mendeliome v0.8496 DPYSL5 Zornitza Stark reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome 4, MIM# 619435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8496 RRP7A Zornitza Stark Phenotypes for gene: RRP7A were changed from Microcephaly to Microcephaly 28, primary, autosomal recessive MIM#619453
Mendeliome v0.8495 RRP7A Zornitza Stark edited their review of gene: RRP7A: Changed phenotypes: Microcephaly 28, primary, autosomal recessive MIM#619453
Mendeliome v0.8495 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Mendeliome v0.8495 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from to Specific granule deficiency, MIM# 245480
Mendeliome v0.8494 CEBPE Zornitza Stark Publications for gene: CEBPE were set to
Mendeliome v0.8493 CEBPE Zornitza Stark Mode of inheritance for gene: CEBPE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8492 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: GREEN; Mode of pathogenicity: None; Publications: 10359588, 11313242, 31256937, 29651288; Phenotypes: Specific granule deficiency, MIM# 245480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8492 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Mendeliome v0.8492 NCF1 Zornitza Stark Phenotypes for gene: NCF1 were changed from to Chronic granulomatous disease 1, autosomal recessive, MIM# 233700
Mendeliome v0.8491 NCF1 Zornitza Stark Publications for gene: NCF1 were set to
Mendeliome v0.8490 NCF1 Zornitza Stark Mode of inheritance for gene: NCF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 NCF1 Zornitza Stark reviewed gene: NCF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2011585, 11133775, 10706888, 16972229, 16972229; Phenotypes: Chronic granulomatous disease 1, autosomal recessive, MIM# 233700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8489 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261; 26486031
Mendeliome v0.8488 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Mendeliome v0.8488 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Mendeliome v0.8487 COL25A1 Zornitza Stark edited their review of gene: COL25A1: Added comment: PMID: 2643702 - Patient: 273182 reported in DECIPHER, chet COL25A1 missense variants (listed as Likely Pathogenic). Phenotype includes Duane anomaly of the eye.

PMID: 31875546 - Mouse models, including Col25a1 KO and muscle-specific KO mice showed a significant reduction in the number of motor neurons in the cranial nerve nuclei, including the oculomotor, trochlear, trigeminal, and facial motor nuclei. Abnormalities in motor innervation of muscles of the head, such as the extraocular and masseter muscles, were also observed

PMID: 31875546 - Functional studies in human cell lines showed that the reported COL25A1 variants (G382R and G497X) impaired the interaction of COL25A1 with receptor protein tyrosine phosphatases, thereby reducing the ability to attract motor axons.; Changed rating: GREEN; Changed publications: 25500261, 26486031, 31875546, 26437029
Mendeliome v0.8487 LTBP1 Zornitza Stark Phenotypes for gene: LTBP1 were changed from cutis laxa syndrome to Cutis laxa, autosomal recessive, type IIE MIM#619451
Mendeliome v0.8486 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease, MIM#619445 to Microvillus inclusion disease, MIM#619445; Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark changed review comment from: At least 5 unrelated families reported.; to: At least 5 unrelated families reported.

STX3 isoform B (STX3B) predominates in the retina, so mutations in the STX3 gene that affect both isoform A (STX3A) and STX3B cause both retinal and gastrointestinal disease (RDMVID), whereas mutations in STX3 affecting only the STX3A transcript cause only diarrhoea.
Mendeliome v0.8485 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445, Retinal dystrophy and microvillus inclusion disease, MIM#619446
Mendeliome v0.8485 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from Microvillus inclusion disease to Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Mendeliome v0.8484 C1QA Zornitza Stark Phenotypes for gene: C1QA were changed from to C1q deficiency, MIM# 613652
Mendeliome v0.8483 C1QA Zornitza Stark Publications for gene: C1QA were set to
Mendeliome v0.8482 C1QA Zornitza Stark Mode of inheritance for gene: C1QA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8481 C1QA Zornitza Stark reviewed gene: C1QA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9225968, 21654842, 9590289; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8481 CIITA Zornitza Stark Marked gene: CIITA as ready
Mendeliome v0.8481 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Mendeliome v0.8481 CIITA Zornitza Stark Phenotypes for gene: CIITA were changed from to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920; varied ID; bronchiolitis; pneumonia; severe autoimmune cytopaenia; CD4 T-cell lymphopaenia; hypogammaglobulinemia; absence of antigen-induced immune response; chronic diarrhoea; recurrent respiratory infections; recurrent gastroenteritis; failure to thrive; liver/biliary tract disease
Mendeliome v0.8480 CIITA Zornitza Stark Publications for gene: CIITA were set to
Mendeliome v0.8479 CIITA Zornitza Stark Mode of inheritance for gene: CIITA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8478 CIITA Zornitza Stark reviewed gene: CIITA: Rating: GREEN; Mode of pathogenicity: None; Publications: 8402893, 9099848, 11862382, 28676232, 24789686, 20197681, 11466404, 15821736, 12910265; Phenotypes: Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920, varied ID, bronchiolitis, pneumonia, severe autoimmune cytopaenia, CD4 T-cell lymphopaenia, hypogammaglobulinemia, absence of antigen-induced immune response, chronic diarrhoea, recurrent respiratory infections, recurrent gastroenteritis, failure to thrive, liver/biliary tract disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8478 CD40LG Zornitza Stark Gene: cd40lg has been classified as Green List (High Evidence).
Mendeliome v0.8478 CD40LG Zornitza Stark Phenotypes for gene: CD40LG were changed from to Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Severe opportunistic infections (recurrent), idiopathic neutropaenia; dysgammaglobulinaemia hepatitis; cholangitis; cholangiocarcinoma; autoimmune blood cytopenias; haemolytic anaemia; thrombocytopaenia; diarrhoea; peripheral neuroectodermal tumours
Mendeliome v0.8477 CD40LG Zornitza Stark Publications for gene: CD40LG were set to
Mendeliome v0.8476 CD40LG Zornitza Stark Mode of inheritance for gene: CD40LG was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8475 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Mendeliome v0.8475 CD3G Zornitza Stark Phenotypes for gene: CD3G were changed from to Immunodeficiency 17, CD3 gamma deficient MIM# 615607; immune deficiency; autoimmunity; failure to thrive; recurrent gastrointestinal infections; recurrent respiratory infections; autoimmune haemolytic anaemia; bronchiolitis obliterans; low CD3 complex; partial T lymphocytopenia; intractable diarrhoea.
Mendeliome v0.8474 CD3G Zornitza Stark Publications for gene: CD3G were set to
Mendeliome v0.8473 CD3G Zornitza Stark Mode of inheritance for gene: CD3G was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8472 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Mendeliome v0.8472 WDR26 Zornitza Stark Mode of inheritance for gene: WDR26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8471 WDR26 Zornitza Stark Publications for gene: WDR26 were set to
Mendeliome v0.8470 WDR26 Zornitza Stark Phenotypes for gene: WDR26 were changed from to Skraban-Deardorff syndrome, MIM#617616
Mendeliome v0.8469 DDB1 Zornitza Stark Phenotypes for gene: DDB1 were changed from Syndromic intellectual disability to White-Kernohan syndrome, MIM# 619426; Syndromic intellectual disability
Mendeliome v0.8468 DDB1 Zornitza Stark edited their review of gene: DDB1: Changed phenotypes: White-Kernohan syndrome, MIM# 619426, Syndromic intellectual disability
Mendeliome v0.8468 CD40LG Danielle Ariti reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7679801, 7679206, 8094231, 9933119, 15358621, 15997875, 7678782, 7915248, 15367912, 7518839, 16311023, 9933119, 12402041, 7882172, 33475257; Phenotypes: mmunodeficiency, X-linked, with hyper-IgM MIM# 308230, Severe opportunistic infections (recurrent), idiopathic neutropaenia, dysgammaglobulinaemia hepatitis, cholangitis, cholangiocarcinoma, autoimmune blood cytopenias, haemolytic anaemia, thrombocytopaenia, diarrhoea, peripheral neuroectodermal tumours; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8468 CD3G Danielle Ariti reviewed gene: CD3G: Rating: GREEN; Mode of pathogenicity: None; Publications: 2872416, 1635567, 17277165, 23590417, 24910257, 18482219, 31921117, 11160319; Phenotypes: Immunodeficiency 17, CD3 gamma deficient MIM# 615607, immune deficiency, autoimmunity, failure to thrive, recurrent gastrointestinal infections, recurrent respiratory infections, autoimmune haemolytic anaemia, bronchiolitis obliterans, low CD3 complex, partial T lymphocytopenia, intractable diarrhoea.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8468 WDR26 Paul De Fazio reviewed gene: WDR26: Rating: GREEN; Mode of pathogenicity: None; Publications: 28686853, 33506510, 33675273; Phenotypes: Skraban-Deardorff syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.8468 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to 22922874; 31113616; 30651581; 28572511
Mendeliome v0.8467 ABCD4 Zornitza Stark reviewed gene: ABCD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type, MIM# 614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8467 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Mendeliome v0.8467 ABCD4 Zornitza Stark Phenotypes for gene: ABCD4 were changed from to Methylmalonic aciduria and homocystinuria, cblJ type MIM#614857
Mendeliome v0.8466 ABCD4 Zornitza Stark Publications for gene: ABCD4 were set to
Mendeliome v0.8465 ABCD4 Zornitza Stark Mode of inheritance for gene: ABCD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8464 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Mendeliome v0.8464 ABCD1 Zornitza Stark Phenotypes for gene: ABCD1 were changed from to Adrenoleukodystrophy MIM#300100
Mendeliome v0.8463 ABCD1 Zornitza Stark Mode of inheritance for gene: ABCD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8462 ABCD1 Zornitza Stark changed review comment from: Ataxia is a feature of this progressive disorder.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.8462 RAD21 Zornitza Stark Phenotypes for gene: RAD21 were changed from ?Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly to Mungan syndrome, 611376; Cornelia de Lange syndrome 4, 614701; Holoprocencephaly
Mendeliome v0.8461 RAD21 Zornitza Stark Publications for gene: RAD21 were set to 31334757; 25575569; 32193685; 31704779
Mendeliome v0.8460 RAD21 Zornitza Stark reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: None; Publications: 14638363, 32193685, 25575569; Phenotypes: Mungan syndrome, MIM# 611376: Barrett esophagus, megaduodenum, cardiac abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8460 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Mendeliome v0.8460 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Mendeliome v0.8459 CCBE1 Zornitza Stark Publications for gene: CCBE1 were set to
Mendeliome v0.8458 CCBE1 Zornitza Stark Mode of inheritance for gene: CCBE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CCBE1 Zornitza Stark reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Mendeliome v0.8457 CD27 Zornitza Stark Phenotypes for gene: CD27 were changed from to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia
Mendeliome v0.8456 CD27 Zornitza Stark Publications for gene: CD27 were set to
Mendeliome v0.8455 CD27 Zornitza Stark Mode of inheritance for gene: CD27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8454 CD27 Zornitza Stark reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, CD27-deficiency MIM# 615122, hepatosplenomegaly, reduced CD8+ T-cell function, lymphadenopathy, hepatosplenomegaly, fever, increased susceptibility to EBV infection, aplastic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8454 ZNF148 Zornitza Stark Classified gene: ZNF148 as Green List (high evidence)
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8452 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Mendeliome v0.8451 PCLO Zornitza Stark Publications for gene: PCLO were set to
Mendeliome v0.8450 PCLO Zornitza Stark Mode of inheritance for gene: PCLO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8449 ZNF148 Natalie Tan gene: ZNF148 was added
gene: ZNF148 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to PMID: 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260
Review for gene: ZNF148 was set to GREEN
Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date.
Sources: Literature
Mendeliome v0.8449 RAC3 Natalie Tan gene: RAC3 was added
gene: RAC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to PMID: 30293988; 29276006
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Multiple unrelated individuals with heterozygous missense variants and a concordant phenotype (severe intellectual disability with brain malformations). No functional studies to date.
Sources: Literature
Mendeliome v0.8449 CHRNA4 Zornitza Stark Gene: chrna4 has been classified as Green List (High Evidence).
Mendeliome v0.8449 CHRNA4 Zornitza Stark Phenotypes for gene: CHRNA4 were changed from to Epilepsy, nocturnal frontal lobe, 1, MIM# 600513
Mendeliome v0.8448 CHRNA4 Zornitza Stark Publications for gene: CHRNA4 were set to
Mendeliome v0.8447 CHRNA4 Zornitza Stark Mode of pathogenicity for gene: CHRNA4 was changed from to Other
Mendeliome v0.8446 CHRNA4 Zornitza Stark Mode of inheritance for gene: CHRNA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8445 CHRNA4 Zornitza Stark reviewed gene: CHRNA4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 14623738, 23114665; Phenotypes: Epilepsy, nocturnal frontal lobe, 1, MIM# 600513; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8445 SYP Elena Savva reviewed gene: SYP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23966691, 19377476; Phenotypes: Mental retardation, X-linked 96 MIM#300802; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8445 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Mendeliome v0.8445 ZIC3 Zornitza Stark Phenotypes for gene: ZIC3 were changed from to Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955); Heterotaxy, visceral, 1, X-linked (MIM#306955); VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8444 ZIC3 Zornitza Stark Publications for gene: ZIC3 were set to
Mendeliome v0.8443 ZIC3 Zornitza Stark Mode of inheritance for gene: ZIC3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed phenotypes: Congenital heart defects, nonsyndromic, 1, X-linked (MIM#306955), Heterotaxy, visceral, 1, X-linked (MIM#306955), VACTERL association, X-linked, MIM# 314390
Mendeliome v0.8442 ZIC3 Zornitza Stark changed review comment from: This gene belongs on the Heterotaxy panel.; to: Well established gene-disease associations.
Mendeliome v0.8442 ZIC3 Zornitza Stark edited their review of gene: ZIC3: Changed rating: GREEN
Mendeliome v0.8442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Mendeliome v0.8442 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome, MIM# 216550
Mendeliome v0.8441 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cohen syndrome, MIM# 216550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8440 VPS13B Zornitza Stark Deleted their review
Mendeliome v0.8440 TULP1 Zornitza Stark Marked gene: TULP1 as ready
Mendeliome v0.8440 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Mendeliome v0.8440 TULP1 Zornitza Stark Phenotypes for gene: TULP1 were changed from to Retinitis pigmentosa 14 M(MIM#600132); Leber congenital amaurosis 15, MIM# 613843
Mendeliome v0.8439 TULP1 Zornitza Stark Publications for gene: TULP1 were set to
Mendeliome v0.8438 TULP1 Zornitza Stark Mode of inheritance for gene: TULP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TULP1 Zornitza Stark commented on gene: TULP1: Several families also reported with LCA.
Mendeliome v0.8437 TULP1 Zornitza Stark edited their review of gene: TULP1: Changed publications: 15024725
Mendeliome v0.8437 TULP1 Zornitza Stark reviewed gene: TULP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 15, MIM# 613843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Mendeliome v0.8437 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Mendeliome v0.8437 TOPORS Zornitza Stark Phenotypes for gene: TOPORS were changed from to Retinitis pigmentosa 31 (MIM#609923)
Mendeliome v0.8436 TOPORS Zornitza Stark Publications for gene: TOPORS were set to
Mendeliome v0.8435 TOPORS Zornitza Stark Mode of inheritance for gene: TOPORS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8434 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Mendeliome v0.8434 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental syndrome; Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8433 SUFU Zornitza Stark Publications for gene: SUFU were set to
Mendeliome v0.8432 SUFU Zornitza Stark Mode of inheritance for gene: SUFU was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Changed phenotypes: Joubert syndrome 32, MIM#617757, SUFU-related neurodevelopmental syndrome, Basal cell nevus syndrome, MIM# 109400
Mendeliome v0.8431 SUFU Zornitza Stark changed review comment from: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome. Note gene also causes dominant Basal Cell Nevus Syndrome.; to: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome.
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Mono-allelic variants are also associated with Basal cell nevus syndrome/predisposition to medulloblastoma.; Changed rating: GREEN; Changed publications: 28965847, 19533801, 31485359; Changed phenotypes: Joubert syndrome 32, MIM#617757, Basal cell nevus syndrome, MIM# 109400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Mendeliome v0.8431 SCNN1G Zornitza Stark Phenotypes for gene: SCNN1G were changed from to Liddle syndrome 2, MIM# 618114; Pseudohypoaldosteronism, type I, MIM# 264350
Mendeliome v0.8430 SCNN1G Zornitza Stark Publications for gene: SCNN1G were set to
Mendeliome v0.8429 SCNN1G Zornitza Stark Mode of inheritance for gene: SCNN1G was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCNN1G Zornitza Stark Deleted their comment
Mendeliome v0.8428 SCNN1G Zornitza Stark edited their review of gene: SCNN1G: Added comment: Variants resulting in constitutive activation of epithelial sodium channel activity have been demonstrated in the beta and gamma subunits as the cause of the autosomal dominant form of hypertension, Liddle syndrome, which is characterized by volume expansion, hypokalemia, and alkalosis.

Variants causing loss of epithelial sodium channel activity cause the converse phenotype of volume depletion, hyperkalaemia and acidosis characteristic of patients with pseudohypoaldosteronism type I.

Well established gene-disease associations.; Changed rating: GREEN; Changed phenotypes: Liddle syndrome 2, MIM# 618114, Pseudohypoaldosteronism, type I, MIM# 264350; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Mendeliome v0.8428 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Mendeliome v0.8428 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Mendeliome v0.8427 SCLT1 Zornitza Stark Publications for gene: SCLT1 were set to
Mendeliome v0.8426 SCLT1 Zornitza Stark Mode of inheritance for gene: SCLT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8425 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Mendeliome v0.8425 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from to Retinitis pigmentosa 3 (MIM#300029)
Mendeliome v0.8424 RPGR Zornitza Stark Publications for gene: RPGR were set to
Mendeliome v0.8423 RPGR Zornitza Stark Mode of inheritance for gene: RPGR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8422 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Mendeliome v0.8422 PRKCSH Zornitza Stark Phenotypes for gene: PRKCSH were changed from to Polycystic liver disease 1 (MIM#174050)
Mendeliome v0.8421 PRKCSH Zornitza Stark Publications for gene: PRKCSH were set to
Mendeliome v0.8420 PRKCSH Zornitza Stark Mode of pathogenicity for gene: PRKCSH was changed from to None
Mendeliome v0.8419 PRKCSH Zornitza Stark Mode of inheritance for gene: PRKCSH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8418 PRKCSH Zornitza Stark reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11047756, 29038287, 12529853, 12577059; Phenotypes: Polycystic liver disease 1 (MIM#174050); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8418 PRKCSH Zornitza Stark Deleted their review
Mendeliome v0.8418 POC1B Zornitza Stark Gene: poc1b has been classified as Green List (High Evidence).
Mendeliome v0.8418 POC1B Zornitza Stark Phenotypes for gene: POC1B were changed from to Cone-rod dystrophy 20 (MIM#615973)
Mendeliome v0.8417 POC1B Zornitza Stark Publications for gene: POC1B were set to
Mendeliome v0.8416 POC1B Zornitza Stark Mode of inheritance for gene: POC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their review
Mendeliome v0.8415 POC1B Zornitza Stark Deleted their comment
Mendeliome v0.8415 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Mendeliome v0.8415 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia (MIM#212065)
Mendeliome v0.8414 PMM2 Zornitza Stark Publications for gene: PMM2 were set to
Mendeliome v0.8413 PMM2 Zornitza Stark Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8412 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Well established gene-disease association.; Changed rating: GREEN; Changed publications: 28108845
Mendeliome v0.8412 PMM2 Zornitza Stark Deleted their comment
Mendeliome v0.8412 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Mendeliome v0.8412 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200
Mendeliome v0.8411 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8410 PKHD1 Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association.
Mendeliome v0.8410 MUC1 Zornitza Stark edited their review of gene: MUC1: Changed publications: 29186029, 29156055, 29520014
Mendeliome v0.8410 MUC1 Zornitza Stark Gene: muc1 has been classified as Green List (High Evidence).
Mendeliome v0.8410 MUC1 Zornitza Stark Phenotypes for gene: MUC1 were changed from to Medullary cystic kidney disease 1 (MIM#174000)
Mendeliome v0.8409 MUC1 Zornitza Stark Publications for gene: MUC1 were set to
Mendeliome v0.8408 MUC1 Zornitza Stark Mode of inheritance for gene: MUC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 MUC1 Zornitza Stark Deleted their comment
Mendeliome v0.8407 MUC1 Zornitza Stark edited their review of gene: MUC1: Added comment: Well established gene-disease association, but note main variant type not readily tractable by NGS.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: Medullary cystic kidney disease 1 (MIM#174000); Changed phenotypes: Medullary cystic kidney disease 1 (MIM#174000); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8407 KIF7 Zornitza Stark Gene: kif7 has been classified as Green List (High Evidence).
Mendeliome v0.8407 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from to Joubert syndrome 12, MIM# 200990; Acrocallosal syndrome, MIM# 200990; MONDO:0008708; Hydrolethalus syndrome 2, MIM# 614120
Mendeliome v0.8406 KIF7 Zornitza Stark Publications for gene: KIF7 were set to
Mendeliome v0.8405 KIF7 Zornitza Stark Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8404 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Mendeliome v0.8404 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from to Orofaciodigital syndrome XV, MIM# 617127; Joubert syndrome
Mendeliome v0.8403 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to
Mendeliome v0.8402 KIAA0753 Zornitza Stark Mode of inheritance for gene: KIAA0753 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed phenotypes: Orofaciodigital syndrome XV 617127, Joubert syndrome; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8401 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed rating: GREEN
Mendeliome v0.8401 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.8401 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23, MIM# 616490; Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546
Mendeliome v0.8400 KIAA0586 Zornitza Stark Publications for gene: KIAA0586 were set to
Mendeliome v0.8399 KIAA0586 Zornitza Stark Mode of inheritance for gene: KIAA0586 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8398 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546, Joubert syndrome
Mendeliome v0.8398 IFT52 Zornitza Stark Marked gene: IFT52 as ready
Mendeliome v0.8398 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Mendeliome v0.8398 IFT52 Zornitza Stark Phenotypes for gene: IFT52 were changed from to Short-rib thoracic dysplasia 16 with or without polydactyly, MIM# 617102
Mendeliome v0.8397 IFT52 Zornitza Stark Publications for gene: IFT52 were set to
Mendeliome v0.8396 IFT52 Zornitza Stark Mode of inheritance for gene: IFT52 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8395 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Mendeliome v0.8395 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Mendeliome v0.8395 IFT27 Zornitza Stark Phenotypes for gene: IFT27 were changed from to Bardet-Biedl syndrome 19, MIM#615996
Mendeliome v0.8394 IFT27 Zornitza Stark Publications for gene: IFT27 were set to
Mendeliome v0.8393 IFT27 Zornitza Stark Mode of inheritance for gene: IFT27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8392 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Phenotypes for gene: POLG2 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131; Mitochondrial DNA depletion syndrome 16 , MIM# 618528
Mendeliome v0.8391 POLG2 Zornitza Stark Publications for gene: POLG2 were set to
Mendeliome v0.8390 POLG2 Zornitza Stark Mode of inheritance for gene: POLG2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8389 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16685652, 21555342, 27592148, 31778857; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8388 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Marked gene: ATP6V0A4 as ready
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Gene: atp6v0a4 has been classified as Green List (High Evidence).
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Phenotypes for gene: ATP6V0A4 were changed from to Renal tubular acidosis, distal, autosomal recessive, MIM#602722
Mendeliome v0.8386 ATP6V0A4 Zornitza Stark Publications for gene: ATP6V0A4 were set to
Mendeliome v0.8385 ATP6V0A4 Zornitza Stark Mode of inheritance for gene: ATP6V0A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ATP6V0A4 Zornitza Stark reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12414817, 10973252; Phenotypes: Renal tubular acidosis, distal, autosomal recessive, MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Mendeliome v0.8384 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia (MIM#612651)
Mendeliome v0.8383 ICK Zornitza Stark Publications for gene: ICK were set to
Mendeliome v0.8382 ICK Zornitza Stark Mode of inheritance for gene: ICK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8381 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Mendeliome v0.8381 HNF1B Zornitza Stark Tag SV/CNV tag was added to gene: HNF1B.
Mendeliome v0.8381 HNF1B Zornitza Stark Phenotypes for gene: HNF1B were changed from to Renal cysts and diabetes syndrome, MIM# 137920
Mendeliome v0.8380 HNF1B Zornitza Stark Mode of inheritance for gene: HNF1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8379 HNF1B Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association, CNVs common.
Mendeliome v0.8379 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Mendeliome v0.8379 GDF1 Zornitza Stark Phenotypes for gene: GDF1 were changed from to Congenital heart defects, multiple types, 6 613854; Right atrial isomerism (Ivemark) 208530
Mendeliome v0.8378 GDF1 Zornitza Stark Publications for gene: GDF1 were set to
Mendeliome v0.8377 GDF1 Zornitza Stark Mode of inheritance for gene: GDF1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8376 GDF1 Zornitza Stark edited their review of gene: GDF1: Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.; Changed rating: GREEN; Changed publications: 32144877; Changed phenotypes: Congenital heart defects, multiple types, 6 613854, Right atrial isomerism (Ivemark) 208530; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8376 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Mendeliome v0.8376 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Mendeliome v0.8375 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Mendeliome v0.8374 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8373 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Mendeliome v0.8373 EVC Zornitza Stark Phenotypes for gene: EVC were changed from to Ellis-van Creveld syndrome, MIM# 225500
Mendeliome v0.8372 EVC Zornitza Stark Publications for gene: EVC were set to
Mendeliome v0.8371 EVC Zornitza Stark Mode of inheritance for gene: EVC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8370 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394
Mendeliome v0.8369 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Mendeliome v0.8368 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 DCDC2 Zornitza Stark changed review comment from: Only a single case with nephronophthisis, most reports are for cholangitis, though zebrafish model has renal cysts.; to: At least 5 families reported with cholangitis, and two with nephronophthisis, though zebrafish model has renal cysts.
Mendeliome v0.8367 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Changed rating: GREEN; Changed publications: 25557784, 27319779, 27469900; Changed phenotypes: Nephronophthisis 19, MIM# 616217, Sclerosing cholangitis, neonatal, MIM# 617394; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v0.8367 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from to Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217
Mendeliome v0.8366 CRELD1 Zornitza Stark Publications for gene: CRELD1 were set to
Mendeliome v0.8365 CRELD1 Zornitza Stark Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740159; Phenotypes: Atrioventricular septal defect, partial, with heterotaxy syndrome, MIM# 606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8364 CRB2 Zornitza Stark Gene: crb2 has been classified as Green List (High Evidence).
Mendeliome v0.8364 CRB2 Zornitza Stark Phenotypes for gene: CRB2 were changed from to Ventriculomegaly with cystic kidney disease, MIM# 219730; Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8363 CRB2 Zornitza Stark Publications for gene: CRB2 were set to
Mendeliome v0.8362 CRB2 Zornitza Stark Mode of inheritance for gene: CRB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8361 CRB2 Zornitza Stark changed review comment from: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.; to: VM with renal disease: More than 7 unrelated families reported, mouse model. Some have presented predominantly with proteinuria, and some more with a multi-system ciliopathy phenotype, and yet others with RP.

FSGS: at least 4 families and animal model.
Mendeliome v0.8361 CRB2 Zornitza Stark edited their review of gene: CRB2: Changed publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779; Changed phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8361 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Mendeliome v0.8361 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Mendeliome v0.8360 CEP55 Zornitza Stark Publications for gene: CEP55 were set to
Mendeliome v0.8359 CEP55 Zornitza Stark Mode of inheritance for gene: CEP55 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CEP55 Zornitza Stark reviewed gene: CEP55: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Mendeliome v0.8358 CENPF Zornitza Stark Phenotypes for gene: CENPF were changed from to Stromme syndrome (MIM#243605)
Mendeliome v0.8357 CENPF Zornitza Stark Publications for gene: CENPF were set to
Mendeliome v0.8356 CENPF Zornitza Stark Mode of inheritance for gene: CENPF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8355 C8orf37 Zornitza Stark Gene: c8orf37 has been classified as Green List (High Evidence).
Mendeliome v0.8355 C8orf37 Zornitza Stark Phenotypes for gene: C8orf37 were changed from to Bardet-Biedl syndrome 21, MIM#617406; Retinitis pigmentosa 64, MIM#614500
Mendeliome v0.8354 C8orf37 Zornitza Stark Publications for gene: C8orf37 were set to
Mendeliome v0.8353 C8orf37 Zornitza Stark Mode of inheritance for gene: C8orf37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8352 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Mendeliome v0.8352 C2CD3 Zornitza Stark Phenotypes for gene: C2CD3 were changed from to Orofaciodigital syndrome XIV, MIM# 615948; MONDO:0014413
Mendeliome v0.8351 C2CD3 Zornitza Stark Publications for gene: C2CD3 were set to
Mendeliome v0.8350 C2CD3 Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8348 CHRM3 Zornitza Stark Gene: chrm3 has been classified as Green List (High Evidence).
Mendeliome v0.8348 CHRM3 Zornitza Stark Phenotypes for gene: CHRM3 were changed from to Prune belly syndrome, MIM# 100100
Mendeliome v0.8347 CHRM3 Zornitza Stark Publications for gene: CHRM3 were set to
Mendeliome v0.8346 CHRM3 Zornitza Stark Mode of inheritance for gene: CHRM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8345 CHRM3 Zornitza Stark reviewed gene: CHRM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22077972, 31441039; Phenotypes: Prune belly syndrome, MIM# 100100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Gene: arhgap42 has been classified as Red List (Low Evidence).
Mendeliome v0.8345 ARHGAP42 Zornitza Stark gene: ARHGAP42 was added
gene: ARHGAP42 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP42 were set to 34232960
Phenotypes for gene: ARHGAP42 were set to Interstitial lung disease; systemic hypertension; immunological abnormalities
Review for gene: ARHGAP42 was set to RED
Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings.
Sources: Literature
Mendeliome v0.8344 KIAA0556 Zornitza Stark changed review comment from: 5 individuals from two families reported, supportive mouse model.; to: 5 individuals from two families reported, supportive mouse model.

New HGNC approved name is KATNIP.
Mendeliome v0.8344 KIAA0556 Zornitza Stark Tag new gene name tag was added to gene: KIAA0556.
Mendeliome v0.8344 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Mendeliome v0.8344 KIAA0556 Zornitza Stark Phenotypes for gene: KIAA0556 were changed from to Joubert syndrome 26, MIM# 616784
Mendeliome v0.8343 KIAA0556 Zornitza Stark Publications for gene: KIAA0556 were set to
Mendeliome v0.8342 KIAA0556 Zornitza Stark Mode of inheritance for gene: KIAA0556 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8341 KIAA0556 Zornitza Stark reviewed gene: KIAA0556: Rating: GREEN; Mode of pathogenicity: None; Publications: 26714646, 27245168; Phenotypes: Joubert syndrome 26, MIM# 616784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8341 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8340 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# MIM#218330 to Cranioectodermal dysplasia 1, MIM# MIM#218330; MONDO:0021093
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8339 LINGO4 Zornitza Stark Classified gene: LINGO4 as Green List (high evidence)
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Classified gene: ARFGEF3 as Green List (high evidence)
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Phenotypes for gene: IMPDH2 were changed from Dystonia to Neurodevelopmental disorder with dystonia
Mendeliome v0.8336 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Mendeliome v0.8336 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8335 LINGO4 Laura Raiti gene: LINGO4 was added
gene: LINGO4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LINGO4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO4 were set to PMID: 33098801
Phenotypes for gene: LINGO4 were set to Developmental Delay, Intellectual disability, speech disorder
Review for gene: LINGO4 was set to GREEN
Added comment: 3 unrelated individuals
1 x individual compound heterozygous for 2x missense variants:
c.679C>A; c.1262G>A p.Leu227Met; p.Arg421Gln comp het. Phenotype: infancy-onset
generalized dystonia; DD/hypo, ID, speech disorder (isolated plus non-MD symptoms) NDD

1 x individual homozygous for missense variant: c.679C>A p.Leu227Met Phenotype: DD/hypo, ID, speech disorder

1 x individual homozygous for missense variant: c.1673G>A p.Ser558Asn Phenotype: DD/hypo, ID, speech disorder
Sources: Literature
Mendeliome v0.8335 ARFGEF3 Laura Raiti gene: ARFGEF3 was added
gene: ARFGEF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARFGEF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARFGEF3 were set to PMID: 33098801
Phenotypes for gene: ARFGEF3 were set to Dystonia
Review for gene: ARFGEF3 was set to GREEN
Added comment: 3 x unrelated individuals
1 x de novo missense variant: c.6212T>C p.Met2071Thr, phenotype: infancy-onset generalized dystonia (isolated)
1x stop-gain variant c.1773T>G p.Tyr591* (inherited from mosaic mother), phenotype: infancy-onset generalized dystonia (isolated)
1 x de novo missense variant (Gene Matcher) c.250A>C p.Met84Leu childhood-onset generalized dystonia (isolated)
Sources: Literature
Mendeliome v0.8335 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Mendeliome v0.8335 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to 19442771; 19361615; 22499340; 23456818; 27925158
Mendeliome v0.8334 DYNC2H1 Zornitza Stark changed review comment from: More than 50 unrelated families reported.; to: More than 50 unrelated families reported with predominantly skeletal dysplasia.

Association with RP: - Five affected probands with homozygous and compound heterozygous missense and PTC variants - Associated with the NM_001080463.1 transcript (predominant isoform in retina from retinal organoid studies). PMID 32753734
Mendeliome v0.8334 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734; Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127, Non-syndromic retinitis pigmentosa
Mendeliome v0.8334 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 KIF20A Zornitza Stark Gene: kif20a has been classified as Red List (Low Evidence).
Mendeliome v0.8333 KIF20A Zornitza Stark edited their review of gene: KIF20A: Changed rating: RED
Mendeliome v0.8333 KIF20A Zornitza Stark gene: KIF20A was added
gene: KIF20A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF20A were set to 29357359
Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433
Review for gene: KIF20A was set to GREEN
Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene.
Sources: Literature
Mendeliome v0.8332 ACTG2 Zornitza Stark Phenotypes for gene: ACTG2 were changed from Visceral myopathy, MIM#155310 to Visceral myopathy, MIM#155310; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 ACTG2 Zornitza Stark edited their review of gene: ACTG2: Changed phenotypes: Visceral myopathy, MIM#155310, Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 B2M Zornitza Stark Gene: b2m has been classified as Green List (High Evidence).
Mendeliome v0.8331 B2M Zornitza Stark Phenotypes for gene: B2M were changed from to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434; Amyloidosis, familial visceral, MIM# 105200
Mendeliome v0.8330 B2M Zornitza Stark Publications for gene: B2M were set to
Mendeliome v0.8329 B2M Zornitza Stark Mode of inheritance for gene: B2M was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 B2M Zornitza Stark reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 4186801, 16549777, 25702838, 11118151, 6165007, 22693999; Phenotypes: Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c, MONDO:0009434, Amyloidosis, familial visceral, MIM# 105200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Mendeliome v0.8327 AK2 Zornitza Stark Publications for gene: AK2 were set to 19043416
Mendeliome v0.8326 AK2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed publications: 19043416, 19043417
Mendeliome v0.8326 TMEM126A Zornitza Stark Marked gene: TMEM126A as ready
Mendeliome v0.8326 TMEM126A Zornitza Stark Gene: tmem126a has been classified as Green List (High Evidence).
Mendeliome v0.8326 TMEM126A Zornitza Stark Phenotypes for gene: TMEM126A were changed from to Optic atrophy 7, MIM# 612989; MONDO:0013069; Syndromic auditory neuropathy spectrum disorder
Mendeliome v0.8325 TMEM126A Zornitza Stark Publications for gene: TMEM126A were set to
Mendeliome v0.8324 TMEM126A Zornitza Stark Mode of inheritance for gene: TMEM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8323 TMEM126A Zornitza Stark reviewed gene: TMEM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 19327736, 20405026, 22815638, 33879611, 31119195, 30961538; Phenotypes: Optic atrophy 7, MIM# 612989, MONDO:0013069, Syndromic auditory neuropathy spectrum disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8323 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8323 MYC Zornitza Stark Phenotypes for gene: MYC were changed from to Burkitt lymphoma, somatic, MIM# 113970
Mendeliome v0.8322 MYC Zornitza Stark Mode of inheritance for gene: MYC was changed from Unknown to Other
Mendeliome v0.8321 MYC Zornitza Stark Classified gene: MYC as Red List (low evidence)
Mendeliome v0.8321 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8320 MYC Zornitza Stark reviewed gene: MYC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Burkitt lymphoma, somatic, MIM# 113970; Mode of inheritance: Other
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark Marked gene: ATG7 as ready
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8318 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8317 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature
Mendeliome v0.8316 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Mendeliome v0.8316 ADA Zornitza Stark Phenotypes for gene: ADA were changed from to Severe combined immunodeficiency due to ADA deficiency, MIM# 102700; MONDO:0007064
Mendeliome v0.8315 ADA Zornitza Stark Publications for gene: ADA were set to
Mendeliome v0.8314 ADA Zornitza Stark Mode of inheritance for gene: ADA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8313 ADA Zornitza Stark reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 3007108, 3475710, 8178821, 8227344, 2783588; Phenotypes: Severe combined immunodeficiency due to ADA deficiency, MIM# 102700, MONDO:0007064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8312 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8311 KDM3B Zornitza Stark Phenotypes for gene: KDM3B were changed from Intellectual disability; dysmorphic features; short stature to Diets-Jongmans syndrome, MIM# 618846; Intellectual disability; dysmorphic features; short stature
Mendeliome v0.8310 KDM3B Zornitza Stark edited their review of gene: KDM3B: Changed phenotypes: Diets-Jongmans syndrome, MIM# 618846, Intellectual disability, dysmorphic features, short stature
Mendeliome v0.8310 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8310 NYNRIN Zornitza Stark Phenotypes for gene: NYNRIN were changed from to Wilms tumour predisposition
Mendeliome v0.8309 NYNRIN Zornitza Stark Classified gene: NYNRIN as Amber List (moderate evidence)
Mendeliome v0.8309 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8308 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome to FBXW7-related neurodevelopmental syndrome; Wilms tumour predisposition
Mendeliome v0.8307 FBXW7 Zornitza Stark Publications for gene: FBXW7 were set to 33057194
Mendeliome v0.8306 FBXW7 Zornitza Stark reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 26482194; Phenotypes: Wilms tumour predisposition; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8306 NYNRIN Laura Raiti gene: NYNRIN was added
gene: NYNRIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NYNRIN were set to PMID: 30885698
Review for gene: NYNRIN was set to AMBER
Added comment: 3 individuals with Wilms Tumour reported (2 children from 1 family, the 3rd child from a second family).
Biallelic truncating mutations in NYNRIN in three children with Wilms Tumour from two families, each parent was heterozygous for one of the mutations.
One of the affected children had an inguinal hernia and another had epilepsy, hypothyroidism, and intellectual disability.
Sources: Literature
Mendeliome v0.8306 YARS Zornitza Stark Phenotypes for gene: YARS were changed from Charcot-Marie-Tooth disease, dominant intermediate C 608323; Bi-allelic variants: ID, deafness, nystagmus to Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323; MONDO:0012012; Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8305 YARS Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: Mono-allelic disease: More than 5 unrelated families reported.
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8305 YARS Zornitza Stark edited their review of gene: YARS: Changed phenotypes: Charcot-Marie-Tooth disease, dominant intermediate C, MIM# 608323, MONDO:0012012, Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, MIM# 619418
Mendeliome v0.8305 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151; 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: PMID: 33710394
1 Finnish family with a hom splice variant, severe ID. Classed a VUS. No functional evidence; Changed publications: 21734151, 28666327, 33710394
Mendeliome v0.8304 ZC3H14 Zornitza Stark Deleted their comment
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: Two families and a mouse model.; Changed phenotypes: Mental retardation, autosomal recessive 56, OMIM# 617125
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed publications: 21734151, 28666327
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8304 ZC3H14 Zornitza Stark Publications for gene: ZC3H14 were set to 21734151
Mendeliome v0.8303 ZC3H14 Zornitza Stark Mode of inheritance for gene: ZC3H14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8302 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Mendeliome v0.8302 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Classified gene: RING1 as Red List (low evidence)
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Tag SV/CNV tag was added to gene: IRX5.
Mendeliome v0.8300 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from to Hamamy syndrome, MIM# 611174; cone dystrophy, MONDO:0000455
Mendeliome v0.8299 IRX5 Zornitza Stark Publications for gene: IRX5 were set to
Mendeliome v0.8298 IRX5 Zornitza Stark Mode of inheritance for gene: IRX5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8297 IRX5 Zornitza Stark Classified gene: IRX5 as Amber List (moderate evidence)
Mendeliome v0.8297 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX5 Zornitza Stark edited their review of gene: IRX5: Changed rating: AMBER
Mendeliome v0.8296 IRX5 Zornitza Stark reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581230, 27453922; Phenotypes: Hamamy syndrome, MIM# 611174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8296 IRX6 Zornitza Stark reviewed gene: IRX6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX6 Zornitza Stark Classified gene: IRX6 as Amber List (moderate evidence)
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8295 RAB3GAP1 Zornitza Stark Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, MIM# 600118; Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8294 RAB3GAP1 Zornitza Stark Publications for gene: RAB3GAP1 were set to 15696165; 20512159; 23420520
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark changed review comment from: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. Multiple families reported.; to: Warburg micro: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.

Martsolf syndrome is characterised by cataracts, mild to severe ID, dysmorphic features. Two families reported.
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark edited their review of gene: RAB3GAP1: Changed publications: 15696165, 20512159, 23420520, 23420520, 30730599; Changed phenotypes: Warburg micro syndrome 1, MIM# 600118, Martsolf syndrome 2, MIM# 619420
Mendeliome v0.8293 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Red List (Low Evidence).
Mendeliome v0.8293 CXCR2 Zornitza Stark gene: CXCR2 was added
gene: CXCR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CXCR2 were set to 24777453
Phenotypes for gene: CXCR2 were set to WHIM syndrome 2, 619407
Review for gene: CXCR2 was set to RED
Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene.
Sources: Expert list
Mendeliome v0.8292 RING1 Eleanor Williams gene: RING1 was added
gene: RING1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RING1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RING1 were set to 29386386
Phenotypes for gene: RING1 were set to microcephaly; intellectual disability
Review for gene: RING1 was set to RED
Added comment: Not associated with any phenotype in OMIM.

PMID: 29386386 - Pierce et al 2018 - report a 13 yo female with a de novo RING1 p.R95Q variant and syndromic neurodevelopmental disabilities. Early motor and language development were normal but were delayed after the first year of life. Cognitive testing showed a verbal IQ of 55 and a visual performance IQ of 63. Head circumference at birth was -4.9 SD, and -4.2 SD at age 13 which falls into the severe microcephaly category. C. elegans with either the missense mutation or complete knockout of spat-3 (the suggested RING1 ortholog) were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance.
Sources: Literature
Mendeliome v0.8292 RNF2 Eleanor Williams gene: RNF2 was added
gene: RNF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNF2 were set to 33864376
Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation
Review for gene: RNF2 was set to AMBER
Added comment: Not associated with any phenotype in OMIM.

PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Mendeliome v0.8292 IRX5 Eleanor Williams edited their review of gene: IRX5: Changed publications: 33891002, 28041643, 32045705, 22581230, 17230486; Changed phenotypes: cone dystrophy, MONDO:0000455, retinitis pigmentosa, MONDO:0019200
Mendeliome v0.8292 IRX5 Eleanor Williams changed review comment from: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition.

Cone dystrophy
-------------------
PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.; to: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition (PMID: 22581230;17230486)

Duplication of gene
-------------------
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Loss of function/gene
---------
PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa.

PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus).
Mendeliome v0.8292 IRX6 Eleanor Williams changed review comment from: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature; to: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Mendeliome v0.8292 GNB2 Zornitza Stark Publications for gene: GNB2 were set to 31698099
Mendeliome v0.8291 GNB2 Zornitza Stark Classified gene: GNB2 as Green List (high evidence)
Mendeliome v0.8291 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Mendeliome v0.8290 GNB2 Zornitza Stark reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31698099, 33971351, 34183358; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8290 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8289 HID1 Zornitza Stark gene: HID1 was added
gene: HID1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HID1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HID1 were set to 33999436
Phenotypes for gene: HID1 were set to Syndromic infantile encephalopathy; Hypopituitarism
Review for gene: HID1 was set to GREEN
Added comment: 7 individuals from 6 unrelated families reported. Clinical features included: hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy
Sources: Literature
Mendeliome v0.8288 KIF1B Zornitza Stark Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8288 KIF1B Zornitza Stark Phenotypes for gene: KIF1B were changed from to Charcot-Marie-Tooth disease, type 2A1 MIM#118210; Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay
Mendeliome v0.8287 KIF1B Zornitza Stark Publications for gene: KIF1B were set to
Mendeliome v0.8286 KIF1B Zornitza Stark Mode of inheritance for gene: KIF1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8285 KIF1B Zornitza Stark reviewed gene: KIF1B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8285 NUF2 Zornitza Stark Classified gene: NUF2 as Red List (low evidence)
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Classified gene: ERGIC3 as Amber List (moderate evidence)
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Phenotypes for gene: FYCO1 were changed from to Cataract 18, MIM#610019
Mendeliome v0.8282 FYCO1 Zornitza Stark Publications for gene: FYCO1 were set to
Mendeliome v0.8281 FYCO1 Zornitza Stark Mode of inheritance for gene: FYCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8280 FYCO1 Zornitza Stark reviewed gene: FYCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32355443; Phenotypes: Cataract 18, MIM#610019; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8280 JPH3 Seb Lunke Publications for gene: JPH3 were set to
Mendeliome v0.8279 MYT1 Zornitza Stark Publications for gene: MYT1 were set to 28612832; 32871052; 27358179
Mendeliome v0.8278 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8278 JPH3 Seb Lunke Phenotypes for gene: JPH3 were changed from to Intellectual disability; dystonia
Mendeliome v0.8277 MYT1 Zornitza Stark changed review comment from: Five unrelated individuals reported with variants in this gene and OAV spectrum.; to: Five unrelated individuals reported with variants in this gene and OAV spectrum.

Single individual reported with missense variant as part of an ID cohort, limited evidence for disease association.
Mendeliome v0.8277 JPH3 Seb Lunke Classified gene: JPH3 as Red List (low evidence)
Mendeliome v0.8277 JPH3 Seb Lunke Added comment: Comment on list classification: Only STRs disease causing, see separate STR list. No evidence for SNVs etc.
Mendeliome v0.8277 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark edited their review of gene: MYT1: Changed publications: 28612832, 32871052, 27358179, 33710394
Mendeliome v0.8276 MYT1 Zornitza Stark Marked gene: MYT1 as ready
Mendeliome v0.8276 MYT1 Zornitza Stark Gene: myt1 has been classified as Green List (High Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark Phenotypes for gene: MYT1 were changed from to Craniofacial microsomia; OAV spectrum
Mendeliome v0.8275 MYT1 Zornitza Stark Publications for gene: MYT1 were set to
Mendeliome v0.8274 MYT1 Zornitza Stark Mode of inheritance for gene: MYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8273 MYT1 Zornitza Stark reviewed gene: MYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28612832, 32871052, 27358179; Phenotypes: Craniofacial microsomia, OAV spectrum; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8273 HEATR5B Seb Lunke Phenotypes for gene: HEATR5B were changed from pontocerebellar hypoplasia to pontocerebellar hypoplasia; intellectual disability; seizures
Mendeliome v0.8272 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8271 ATP1A2 Zornitza Stark Publications for gene: ATP1A2 were set to
Mendeliome v0.8270 ATP1A2 Zornitza Stark Mode of inheritance for gene: ATP1A2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: Association with alternating hemiplegia is well established.

PMID 31608932: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal.

PMID 33880529: six individuals with de novo missense variants reported and DD/EE/PMG.; Changed rating: GREEN; Changed publications: 31608932, 33880529; Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations, Developmental and epileptic encephalopathy, polymicrogyria; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 HEATR5B Seb Lunke Marked gene: HEATR5B as ready
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8269 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed phenotypes: Alternating hemiplegia of childhood 2, MIM# 614820, CAPOS syndrome, MIM# 601338, Dystonia-12, MIM# 128235, Polymicrogyria, Developmental and epileptic encephalopathy
Mendeliome v0.8268 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed publications: 15260953, 22842232, 24468074, 33762331, 33880529
Mendeliome v0.8268 SAMD9L Zornitza Stark Phenotypes for gene: SAMD9L were changed from Ataxia-pancytopenia syndrome, MIM# 159550 to Ataxia-pancytopenia syndrome, MIM# 159550; Intellectual disability
Mendeliome v0.8267 SAMD9L Zornitza Stark Publications for gene: SAMD9L were set to 27259050; 30923096; 30322869
Mendeliome v0.8266 SAMD9L Zornitza Stark changed review comment from: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.; to: Ataxia-pancytopaenia: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

ID: single individual reported, limited evidence of association.
Mendeliome v0.8266 SAMD9L Zornitza Stark edited their review of gene: SAMD9L: Changed publications: 27259050, 30923096, 30322869, 33710394
Mendeliome v0.8266 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Ataxia; Intellectual disability to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Mendeliome v0.8265 PITRM1 Zornitza Stark edited their review of gene: PITRM1: Changed phenotypes: Spinocerebellar ataxia-30 (SCAR30), MIM#619405
Mendeliome v0.8265 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.8264 IRX6 Eleanor Williams gene: IRX6 was added
gene: IRX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRX6 were set to 33891002
Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455
Mode of pathogenicity for gene: IRX6 was set to Other
Review for gene: IRX6 was set to GREEN
Added comment: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8264 IRX5 Eleanor Williams reviewed gene: IRX5: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33891002; Phenotypes: cone dystrophy, MONDO:0000455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8264 EPHA7 Zornitza Stark Tag SV/CNV tag was added to gene: EPHA7.
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8264 EPHA7 Zornitza Stark Classified gene: EPHA7 as Amber List (moderate evidence)
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8263 EPHA7 Zornitza Stark gene: EPHA7 was added
gene: EPHA7 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA7 were set to 34176129
Phenotypes for gene: EPHA7 were set to Intellectual disability
Review for gene: EPHA7 was set to AMBER
Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder.

The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7.

Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%).

The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7.

9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one.

The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function).

Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs.

Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1].
Sources: Expert Review
Mendeliome v0.8262 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Mendeliome v0.8262 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from to Developmental and epileptic encephalopathy 31, OMIM:616346
Mendeliome v0.8261 DNM1 Zornitza Stark Publications for gene: DNM1 were set to
Mendeliome v0.8260 DNM1 Zornitza Stark Mode of inheritance for gene: DNM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 DNM1 Zornitza Stark reviewed gene: DNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25262651, 27066543, 33372033, 34172529; Phenotypes: Developmental and epileptic encephalopathy 31, OMIM:616346; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8259 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8258 GRK2 Zornitza Stark gene: GRK2 was added
gene: GRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GRK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRK2 were set to 33200460
Phenotypes for gene: GRK2 were set to Jeune asphyxiating thoracic dystrophy (ATD)
Review for gene: GRK2 was set to AMBER
Added comment: Two unrelated families reported and some functional data.
Sources: Literature
Mendeliome v0.8257 WDR60 Zornitza Stark Gene: wdr60 has been classified as Green List (High Evidence).
Mendeliome v0.8257 WDR60 Zornitza Stark Phenotypes for gene: WDR60 were changed from to Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503; Retinitis pigmentosa
Mendeliome v0.8256 WDR60 Zornitza Stark Publications for gene: WDR60 were set to
Mendeliome v0.8255 WDR60 Zornitza Stark Mode of inheritance for gene: WDR60 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8254 WDR60 Zornitza Stark reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: None; Publications: 23910462, 29271569, 26874042; Phenotypes: Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8254 WDR34 Zornitza Stark Gene: wdr34 has been classified as Green List (High Evidence).
Mendeliome v0.8254 WDR34 Zornitza Stark Phenotypes for gene: WDR34 were changed from to Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633; Retinitis pigmentosa
Mendeliome v0.8253 WDR34 Zornitza Stark Publications for gene: WDR34 were set to
Mendeliome v0.8252 WDR34 Zornitza Stark Mode of inheritance for gene: WDR34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8251 WDR34 Zornitza Stark reviewed gene: WDR34: Rating: GREEN; Mode of pathogenicity: None; Publications: 24183449, 24183451, 33124039, 30649997, 29241935, 28379358; Phenotypes: Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8251 WDR19 Zornitza Stark Gene: wdr19 has been classified as Green List (High Evidence).
Mendeliome v0.8251 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378
Mendeliome v0.8250 WDR19 Zornitza Stark Publications for gene: WDR19 were set to
Mendeliome v0.8249 WDR19 Zornitza Stark Mode of inheritance for gene: WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8248 WDR19 Zornitza Stark reviewed gene: WDR19: Rating: GREEN; Mode of pathogenicity: None; Publications: 33946315, 33875766, 33606107, 22019273, 23559409, 23683095, 32055034; Phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307, Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376, Cranioectodermal dysplasia 4, MIM# 614378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8248 TXNDC15 Zornitza Stark Marked gene: TXNDC15 as ready
Mendeliome v0.8248 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Mendeliome v0.8248 TXNDC15 Zornitza Stark Phenotypes for gene: TXNDC15 were changed from to Meckel-Gruber syndrome
Mendeliome v0.8247 TXNDC15 Zornitza Stark Publications for gene: TXNDC15 were set to
Mendeliome v0.8246 TXNDC15 Zornitza Stark Mode of inheritance for gene: TXNDC15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8245 TXNDC15 Zornitza Stark reviewed gene: TXNDC15: Rating: GREEN; Mode of pathogenicity: None; Publications: 30851085, 27894351; Phenotypes: Meckel-Gruber syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8245 TTC8 Zornitza Stark Marked gene: TTC8 as ready
Mendeliome v0.8245 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Mendeliome v0.8245 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from to Bardet-Biedl syndrome 8, MIM# 615985
Mendeliome v0.8244 TTC8 Zornitza Stark Publications for gene: TTC8 were set to
Mendeliome v0.8243 TTC8 Zornitza Stark Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8242 TTC8 Zornitza Stark reviewed gene: TTC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 14520415, 19797195; Phenotypes: Bardet-Biedl syndrome 8, MIM# 615985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8242 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Mendeliome v0.8242 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Mendeliome v0.8242 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome
Mendeliome v0.8241 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Mendeliome v0.8240 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TTC21B Zornitza Stark reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258341, 25492405, 18327258, 33875766; Phenotypes: Nephronophthisis 12, MIM# 613820, Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819, Joubert syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Marked gene: TRAF3IP1 as ready
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Gene: traf3ip1 has been classified as Green List (High Evidence).
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Phenotypes for gene: TRAF3IP1 were changed from to Senior-Loken syndrome 9, MIM# 616629; MONDO:0014712
Mendeliome v0.8238 TRAF3IP1 Zornitza Stark Publications for gene: TRAF3IP1 were set to
Mendeliome v0.8237 TRAF3IP1 Zornitza Stark Mode of inheritance for gene: TRAF3IP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8236 TRAF3IP1 Zornitza Stark reviewed gene: TRAF3IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26487268, 18364699, 21945076; Phenotypes: Senior-Loken syndrome 9, MIM# 616629, MONDO:0014712; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8236 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Mendeliome v0.8236 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8235 ATP2C2 Zornitza Stark Classified gene: ATP2C2 as Red List (low evidence)
Mendeliome v0.8235 ATP2C2 Zornitza Stark Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.8234 OBSCN Zornitza Stark Tag refuted was removed from gene: OBSCN.
Tag disputed tag was added to gene: OBSCN.
Mendeliome v0.8234 OBSCN Zornitza Stark Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914
Mendeliome v0.8233 OBSCN Zornitza Stark Tag refuted tag was added to gene: OBSCN.
Mendeliome v0.8233 P2RX2 Zornitza Stark Publications for gene: P2RX2 were set to 23345450; 24211385
Mendeliome v0.8232 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33729479; 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 29479578
Mendeliome v0.8231 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33729479; 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 2947957; 8
Mendeliome v0.8230 AP2S1 Zornitza Stark Publications for gene: AP2S1 were set to 33057194; 23222959; 33729479; 33168530; 3204769; 31723423; 29479578
Mendeliome v0.8229 ATP9A Arina Puzriakova gene: ATP9A was added
gene: ATP9A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843
Phenotypes for gene: ATP9A were set to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms
Review for gene: ATP9A was set to AMBER
Added comment: Vogt et al. 2021 report on 3 individuals from 2 unrelated consanguineous families with different homozygous truncating variants in ATP9A, presenting with DD/ID of variable degree (2 mild, 1 severe), postnatal microcephaly (OFC range: −2.33 SD to −3.58 SD), failure to thrive, and gastrointestinal symptoms. Patient-derived fibroblasts showed reduced expression of ATP9A, and consistent with previous findings also overexpression of interacting partners, ARPC3 and SNX3.
Sources: Literature
Mendeliome v0.8229 ATP2C2 Eleanor Williams gene: ATP2C2 was added
gene: ATP2C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP2C2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP2C2 were set to 33864365; 28440294
Phenotypes for gene: ATP2C2 were set to language impairment, HP:0002463
Review for gene: ATP2C2 was set to RED
Added comment: PMID: 33864365 - Martinelli et al 2021 - report a family with a missense variant NM_001286527.2:c.304G>A, p.(Val102Met) in ATP2C2 in a father and two siblings with specific language impairment. However two other affected siblings did not have this variant. This variant was also reported by Chen et al. They found that the variant had a higher frequency in language cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). They postulate that variant is not sufficient on its own to cause a disorder but is a susceptibility factor which increases the risk for language impairment.

PMID: 28440294 - Chen et al 2017 - report 2 probands with severe learning impairment, and missense variants in ATP2C2 (NM_001286527: c.G304A:p.V102M and NM_001291454:exon21: c.C1936T:p.R646W).
Sources: Literature
Mendeliome v0.8229 OBSCN Eleanor Williams reviewed gene: OBSCN: Rating: RED; Mode of pathogenicity: None; Publications: 33438037; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 P2RX2 Eleanor Williams reviewed gene: P2RX2: Rating: ; Mode of pathogenicity: None; Publications: 33791800; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 AP2S1 Eleanor Williams reviewed gene: AP2S1: Rating: ; Mode of pathogenicity: None; Publications: 33729479; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.8229 TMEM67 Zornitza Stark Marked gene: TMEM67 as ready
Mendeliome v0.8229 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Green List (High Evidence).
Mendeliome v0.8229 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from to Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361; Nephronophthisis 11, MIM# 613550; COACH syndrome 1, MIM# 216360
Mendeliome v0.8228 TMEM67 Zornitza Stark Publications for gene: TMEM67 were set to
Mendeliome v0.8227 TMEM67 Zornitza Stark Mode of inheritance for gene: TMEM67 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8226 TMEM67 Zornitza Stark Deleted their comment
Mendeliome v0.8226 TMEM67 Zornitza Stark edited their review of gene: TMEM67: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS, Meckel syndrome and nephronophthisis. Multiple families with each.; Changed publications: 16415887, 17377820, 17160906, 19508969; Changed phenotypes: Joubert syndrome 6, MIM# 610688, Meckel syndrome 3, MIM# 607361, Nephronophthisis 11, MIM# 613550, COACH syndrome 1, MIM# 216360
Mendeliome v0.8226 XDH Zornitza Stark Gene: xdh has been classified as Green List (High Evidence).
Mendeliome v0.8226 XDH Zornitza Stark Phenotypes for gene: XDH were changed from to Xanthinuria, type I (MIM#278300)
Mendeliome v0.8225 XDH Zornitza Stark Publications for gene: XDH were set to
Mendeliome v0.8224 XDH Zornitza Stark Mode of inheritance for gene: XDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8223 XDH Ain Roesley reviewed gene: XDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32071838; Phenotypes: Xanthinuria, type I (MIM#278300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Marked gene: TCTEX1D2 as ready
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Gene: tctex1d2 has been classified as Green List (High Evidence).
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Phenotypes for gene: TCTEX1D2 were changed from to Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405
Mendeliome v0.8222 TCTEX1D2 Zornitza Stark Publications for gene: TCTEX1D2 were set to
Mendeliome v0.8221 TCTEX1D2 Zornitza Stark Mode of inheritance for gene: TCTEX1D2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8220 TCTEX1D2 Zornitza Stark reviewed gene: TCTEX1D2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26044572, 25830415; Phenotypes: Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8220 TCTN3 Zornitza Stark Marked gene: TCTN3 as ready
Mendeliome v0.8220 TCTN3 Zornitza Stark Gene: tctn3 has been classified as Green List (High Evidence).
Mendeliome v0.8220 TCTN3 Zornitza Stark Phenotypes for gene: TCTN3 were changed from to Joubert syndrome 18, MIM# 614815; MONDO:0013896; Orofaciodigital syndrome IV, MIM# 258860; Mohr-Majewski syndrome; Meckel-Gruber syndrome
Mendeliome v0.8219 TCTN3 Zornitza Stark Publications for gene: TCTN3 were set to
Mendeliome v0.8218 TCTN3 Zornitza Stark Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8217 TCTN3 Zornitza Stark changed review comment from: Rare cause of JBS, I can only find two families reported plus one with OFD. Ataxia specifically described in one of the JBS individuals.; to: Three unrelated families reported with JBTS phenotype. Variants in this gene are associated with other ciliopathies as well (OFD and Mohr-Majewski).
Mendeliome v0.8217 TCTN3 Zornitza Stark edited their review of gene: TCTN3: Changed publications: 22883145, 32139166, 25118024, 34096792; Changed phenotypes: Joubert syndrome 18, MIM# 614815, MONDO:0013896, Orofaciodigital syndrome IV, MIM# 258860, Mohr-Majewski syndrome, Meckel-Gruber syndrome
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis
Mendeliome v0.8216 SDCCAG8 Zornitza Stark Publications for gene: SDCCAG8 were set to
Mendeliome v0.8215 SDCCAG8 Zornitza Stark Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8214 SDCCAG8 Zornitza Stark reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20835237, 22626039, 22626039, 32432520, 31534065, 26968886; Phenotypes: Bardet-Biedl syndrome 16, MIM# 615993, MONDO:0014444, Senior-Loken syndrome 7, MIM# 613615, MONDO:0013326, Nephronophthisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8214 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Mendeliome v0.8214 SBDS Zornitza Stark Phenotypes for gene: SBDS were changed from to Shwachman-Diamond syndrome, MIM# 260400
Mendeliome v0.8213 SBDS Zornitza Stark Mode of inheritance for gene: SBDS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8212 SBDS Zornitza Stark reviewed gene: SBDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Shwachman-Diamond syndrome, MIM# 260400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Deleted their comment
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Nephronophthisis
Mendeliome v0.8211 RPGRIP1L Zornitza Stark Publications for gene: RPGRIP1L were set to
Mendeliome v0.8210 RPGRIP1L Zornitza Stark Mode of inheritance for gene: RPGRIP1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8209 RPGRIP1L Zornitza Stark edited their review of gene: RPGRIP1L: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS and Meckel syndrome. Mouse model.; Changed publications: 17558409, 17558407, 17960139, 26071364, 19574260, 29991045; Changed phenotypes: Joubert syndrome 7, MIM# 611560, Meckel syndrome 5, MIM# 611561, COACH syndrome 3, MIM# 619113, Nephronophthisis
Mendeliome v0.8209 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Mendeliome v0.8209 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Mendeliome v0.8208 NPHP4 Zornitza Stark Publications for gene: NPHP4 were set to
Mendeliome v0.8207 NPHP4 Zornitza Stark Mode of inheritance for gene: NPHP4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8206 NPHP4 Zornitza Stark reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113; Phenotypes: Nephronophthisis 4, MIM# 606966, Senior-Loken syndrome 4, MIM# 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8206 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Mendeliome v0.8206 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from to Joubert syndrome 4, MIM# 609583; Nephronophthisis 1, juvenile, MIM# 256100; Senior-Loken syndrome-1, MIM# 266900
Mendeliome v0.8205 NPHP1 Zornitza Stark Publications for gene: NPHP1 were set to
Mendeliome v0.8204 NPHP1 Zornitza Stark Mode of inheritance for gene: NPHP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8203 NPHP1 Zornitza Stark Tag SV/CNV tag was added to gene: NPHP1.
Mendeliome v0.8203 NPHP1 Zornitza Stark reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15138899, 32139166, 28347285, 8852662, 9856524; Phenotypes: Joubert syndrome 4, MIM# 609583, Nephronophthisis 1, juvenile, MIM# 256100, Senior-Loken syndrome-1, MIM# 266900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8203 TIE1 Zornitza Stark Marked gene: TIE1 as ready
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8203 TIE1 Zornitza Stark Classified gene: TIE1 as Amber List (moderate evidence)
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8202 TIE1 Zornitza Stark gene: TIE1 was added
gene: TIE1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TIE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TIE1 were set to 32947856; 24764452
Phenotypes for gene: TIE1 were set to Lymphatic malformation 11, MIM# 619401
Review for gene: TIE1 was set to AMBER
Added comment: Three families reported, supportive animal model, though variants are missense and present at a low frequency in gnomad.
Sources: Literature
Mendeliome v0.8201 KIF1B Paul De Fazio reviewed gene: KIF1B: Rating: RED; Mode of pathogenicity: None; Publications: 33710394; Phenotypes: Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8201 NUF2 Dean Phelan gene: NUF2 was added
gene: NUF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to PMID: 33721060
Phenotypes for gene: NUF2 were set to microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Literature
Mendeliome v0.8201 ERGIC3 Elena Savva gene: ERGIC3 was added
gene: ERGIC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERGIC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC3 were set to PMID: 33710394; 31585110
Phenotypes for gene: ERGIC3 were set to Intellectual disability
Review for gene: ERGIC3 was set to AMBER
Added comment: PMID: 33710394 - two homozygous sibs with mild ID, a novel canonical splice (c.717+1G>A). Absent in gnomAD, no splice studies. Classed as a VUS.

PMID: 31585110 - 1 hom (p.Gln233Argfs*10) in a male 8yo with Growth retardation, Microcephaly, Learning disability, Facial dysmorphism, Abnormal pigmentation.
Sources: Literature
Mendeliome v0.8201 JPH3 Teresa Zhao reviewed gene: JPH3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33824468; Phenotypes: Huntington disease-like 2 (MIM#606438) AD; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8201 HEATR5B Teresa Zhao gene: HEATR5B was added
gene: HEATR5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to PMID: 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay.

Two homozygous splice variants were reported ((c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated
with reduced levels of HEATR5B protein.

Homozygous knockout mice were not viable.

*NOTE: gene (and alias) not found in OMIM
Sources: Literature
Mendeliome v0.8201 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Mendeliome v0.8201 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174
Mendeliome v0.8200 NEK8 Zornitza Stark Publications for gene: NEK8 were set to
Mendeliome v0.8199 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8198 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 33131162, 23418306, 26862157, 26697755, 26967905, 23274954, 31633649; Phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8198 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Mendeliome v0.8198 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa
Mendeliome v0.8197 MKKS Zornitza Stark Publications for gene: MKKS were set to
Mendeliome v0.8196 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8195 MKKS Zornitza Stark reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802661, 26900326, 10973251; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome, MIM# 236700, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8195 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Green List (High Evidence).
Mendeliome v0.8195 IQCB1 Zornitza Stark Phenotypes for gene: IQCB1 were changed from to Senior-Loken syndrome 5, MIM# 609254; MONDO:0012225
Mendeliome v0.8194 IQCB1 Zornitza Stark Publications for gene: IQCB1 were set to
Mendeliome v0.8193 IQCB1 Zornitza Stark Mode of inheritance for gene: IQCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8192 IQCB1 Zornitza Stark reviewed gene: IQCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15723066, 21220633, 20881296, 21901789, 33512896, 33535056, 29219953; Phenotypes: Senior-Loken syndrome 5, MIM# 609254, MONDO:0012225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8192 IFT80 Zornitza Stark Marked gene: IFT80 as ready
Mendeliome v0.8192 IFT80 Zornitza Stark Gene: ift80 has been classified as Green List (High Evidence).
Mendeliome v0.8192 IFT80 Zornitza Stark Phenotypes for gene: IFT80 were changed from to Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263; MONDO:0012644
Mendeliome v0.8191 IFT80 Zornitza Stark Publications for gene: IFT80 were set to
Mendeliome v0.8190 IFT80 Zornitza Stark Mode of inheritance for gene: IFT80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8189 IFT80 Zornitza Stark commented on gene: IFT80: 5 unrelated families reported.
Mendeliome v0.8189 IFT80 Zornitza Stark reviewed gene: IFT80: Rating: GREEN; Mode of pathogenicity: None; Publications: 17468754, 19648123, 30767363; Phenotypes: Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263, MONDO:0012644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8189 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Mendeliome v0.8189 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Mendeliome v0.8189 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from to Bardet-Biedl syndrome 17 (MIM#615994)
Mendeliome v0.8188 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Mendeliome v0.8187 LZTFL1 Zornitza Stark Mode of inheritance for gene: LZTFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8186 LZTFL1 Zornitza Stark reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011, 22072986; Phenotypes: Bardet-Biedl syndrome 17 (MIM#615994); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8186 TTC26 Zornitza Stark changed review comment from: Seven families and functional data including zebrafish model.
Sources: Literature; to: Nine families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8186 TTC26 Zornitza Stark changed review comment from: Three unrelated families and functional data including zebrafish model.
Sources: Literature; to: Seven families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8186 TTC26 Zornitza Stark Marked gene: TTC26 as ready
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8186 TTC26 Zornitza Stark Classified gene: TTC26 as Green List (high evidence)
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8185 TTC26 Zornitza Stark gene: TTC26 was added
gene: TTC26 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903
Phenotypes for gene: TTC26 were set to Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Review for gene: TTC26 was set to GREEN
Added comment: Three unrelated families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8184 IFT43 Zornitza Stark Publications for gene: IFT43 were set to 28400947; 28973684; 21378380
Mendeliome v0.8183 IFT43 Zornitza Stark changed review comment from: One family reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.; to: Two families reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.
Mendeliome v0.8183 IFT43 Zornitza Stark edited their review of gene: IFT43: Changed publications: 28400947, 28973684, 21378380, 29896747
Mendeliome v0.8183 IFT43 Zornitza Stark Marked gene: IFT43 as ready
Mendeliome v0.8183 IFT43 Zornitza Stark Gene: ift43 has been classified as Green List (High Evidence).
Mendeliome v0.8183 IFT43 Zornitza Stark Phenotypes for gene: IFT43 were changed from to Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866; Retinitis pigmentosa 81 , MIM#617871; Cranioectodermal dysplasia 3, MIM# 614099
Mendeliome v0.8182 IFT43 Zornitza Stark Publications for gene: IFT43 were set to
Mendeliome v0.8181 IFT43 Zornitza Stark Mode of inheritance for gene: IFT43 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8180 IFT43 Zornitza Stark reviewed gene: IFT43: Rating: GREEN; Mode of pathogenicity: None; Publications: 28400947, 28973684, 21378380; Phenotypes: Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866, Retinitis pigmentosa 81 , MIM#617871, Cranioectodermal dysplasia 3, MIM# 614099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8180 IFT140 Zornitza Stark Marked gene: IFT140 as ready
Mendeliome v0.8180 IFT140 Zornitza Stark Gene: ift140 has been classified as Green List (High Evidence).
Mendeliome v0.8180 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8179 IFT140 Zornitza Stark Publications for gene: IFT140 were set to
Mendeliome v0.8178 IFT140 Zornitza Stark Mode of inheritance for gene: IFT140 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8177 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 28288023, 28724397, 26216056, 26968735; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8177 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.8176 SNORA31 Zornitza Stark Phenotypes for gene: SNORA31 were changed from Susceptibility to HSV1 encephalitis to {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}, MIM# 619396
Mendeliome v0.8175 SNORA31 Zornitza Stark edited their review of gene: SNORA31: Changed phenotypes: {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}, MIM# 619396
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; MONDO:0013127
Mendeliome v0.8174 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to
Mendeliome v0.8173 DYNC2H1 Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19442771, 19361615, 22499340, 23456818, 27925158; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Mendeliome v0.8172 DDX59 Zornitza Stark Phenotypes for gene: DDX59 were changed from to Orofaciodigital syndrome V (MIM#174300)
Mendeliome v0.8171 DDX59 Zornitza Stark Publications for gene: DDX59 were set to
Mendeliome v0.8170 DDX59 Zornitza Stark Mode of inheritance for gene: DDX59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8169 DDX59 Zornitza Stark reviewed gene: DDX59: Rating: GREEN; Mode of pathogenicity: None; Publications: 29127725, 23972372, 28711741; Phenotypes: Orofaciodigital syndrome V (MIM#174300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8169 CEP83 Zornitza Stark Gene: cep83 has been classified as Green List (High Evidence).
Mendeliome v0.8169 CEP83 Zornitza Stark Phenotypes for gene: CEP83 were changed from to Nephronophthisis 18, MIM# 615862; MONDO:0014374; Retinal dystrophy; ID
Mendeliome v0.8168 CEP83 Zornitza Stark Publications for gene: CEP83 were set to
Mendeliome v0.8167 CEP83 Zornitza Stark Mode of inheritance for gene: CEP83 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8166 CEP83 Zornitza Stark reviewed gene: CEP83: Rating: GREEN; Mode of pathogenicity: None; Publications: 24882706, 33938610; Phenotypes: Nephronophthisis 18, MIM# 615862, MONDO:0014374, Retinal dystrophy, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8166 RNU12 Bryony Thompson Classified gene: RNU12 as Green List (high evidence)
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8165 RNU12 Bryony Thompson gene: RNU12 was added
gene: RNU12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356; 27863452
Phenotypes for gene: RNU12 were set to CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations
Review for gene: RNU12 was set to GREEN
Added comment: 5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events. Also, limited evidence for an association with cerebellar ataxia with a single large consanguineous family reported with a homozygous variant.
Sources: Literature
Mendeliome v0.8164 FHOD3 Zornitza Stark Gene: fhod3 has been classified as Green List (High Evidence).
Mendeliome v0.8164 FHOD3 Zornitza Stark Phenotypes for gene: FHOD3 were changed from to Cardiomyopathy, familial hypertrophic, 28, MIM# 619402
Mendeliome v0.8163 FHOD3 Zornitza Stark Publications for gene: FHOD3 were set to
Mendeliome v0.8162 FHOD3 Zornitza Stark Mode of inheritance for gene: FHOD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8161 FHOD3 Zornitza Stark Tag SV/CNV tag was added to gene: FHOD3.
Mendeliome v0.8161 FHOD3 Zornitza Stark reviewed gene: FHOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32335906, 31742804, 30442288; Phenotypes: Cardiomyopathy, familial hypertrophic, 28, MIM# 619402; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8161 PPP1R21 Zornitza Stark Phenotypes for gene: PPP1R21 were changed from Hypotonia; intellectual disability; white matter abnormalities to Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, MIM# 619383; Hypotonia; intellectual disability; white matter abnormalities
Mendeliome v0.8160 PPP1R21 Zornitza Stark edited their review of gene: PPP1R21: Changed phenotypes: Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, MIM# 619383, Hypotonia, intellectual disability, white matter abnormalities
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8160 KCNJ16 Zornitza Stark Classified gene: KCNJ16 as Green List (high evidence)
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8159 KCNJ16 Zornitza Stark gene: KCNJ16 was added
gene: KCNJ16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNJ16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ16 were set to 33811157; 33840812
Phenotypes for gene: KCNJ16 were set to Renal tubulopathy; deafness
Review for gene: KCNJ16 was set to GREEN
Added comment: 8 unrelated families reported.
Sources: Literature
Mendeliome v0.8158 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Mendeliome v0.8158 KLHL7 Zornitza Stark Phenotypes for gene: KLHL7 were changed from to PERCHING syndrome (MIM#617055); Retinitis pigmentosa 42 (MIM#612943)
Mendeliome v0.8157 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Mendeliome v0.8156 KLHL7 Zornitza Stark Mode of inheritance for gene: KLHL7 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.8155 SLC34A3 Zornitza Stark Gene: slc34a3 has been classified as Green List (High Evidence).
Mendeliome v0.8155 SLC34A3 Zornitza Stark Phenotypes for gene: SLC34A3 were changed from to Hypophosphatemic rickets with hypercalciuria, (MIM#241530)
Mendeliome v0.8154 SLC34A3 Zornitza Stark Publications for gene: SLC34A3 were set to
Mendeliome v0.8153 SLC34A3 Zornitza Stark Mode of inheritance for gene: SLC34A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8152 TNC Zornitza Stark Marked gene: TNC as ready
Mendeliome v0.8152 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8152 TNC Zornitza Stark Phenotypes for gene: TNC were changed from to Deafness, autosomal dominant 56, MIM# 615629
Mendeliome v0.8151 TNC Zornitza Stark Publications for gene: TNC were set to
Mendeliome v0.8150 TNC Zornitza Stark Mode of inheritance for gene: TNC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8149 TNC Zornitza Stark Classified gene: TNC as Amber List (moderate evidence)
Mendeliome v0.8149 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8148 TNC Zornitza Stark reviewed gene: TNC: Rating: AMBER; Mode of pathogenicity: None; Publications: 23936043, 34093110, 33763067; Phenotypes: Deafness, autosomal dominant 56, MIM# 615629; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8148 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Mendeliome v0.8148 RIPK4 Zornitza Stark Phenotypes for gene: RIPK4 were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650
Mendeliome v0.8147 RIPK4 Zornitza Stark Publications for gene: RIPK4 were set to
Mendeliome v0.8146 RIPK4 Zornitza Stark Mode of inheritance for gene: RIPK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 RIPK4 Zornitza Stark reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940926, 22197489, 22197488; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type, MIM# 263650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 KLHL7 Ain Roesley reviewed gene: KLHL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953236, 30300710, 31856884; Phenotypes: PERCHING syndrome (MIM#617055), Retinitis pigmentosa 42 (MIM#612943); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8145 SLC34A3 Ain Roesley reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32524022; Phenotypes: Hypophosphatemic rickets with hypercalciuria, (MIM#241530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8145 CEP290 Zornitza Stark Gene: cep290 has been classified as Green List (High Evidence).
Mendeliome v0.8145 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Meckel syndrome 4, MIM# 611134; Senior-Loken syndrome 6, MIM# 610189
Mendeliome v0.8144 CEP290 Zornitza Stark Publications for gene: CEP290 were set to
Mendeliome v0.8143 CEP290 Zornitza Stark Mode of inheritance for gene: CEP290 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8142 CEP290 Zornitza Stark reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 20690115, 16682973, 16682970, 17564967, 16909394, 17564974; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8142 CEP164 Zornitza Stark Gene: cep164 has been classified as Green List (High Evidence).
Mendeliome v0.8142 CEP164 Zornitza Stark Phenotypes for gene: CEP164 were changed from to Bardet-Biedl syndrome; Nephronophthisis 15, MIM# 614845; Oro-facio-digital syndrome
Mendeliome v0.8141 CEP164 Zornitza Stark Publications for gene: CEP164 were set to
Mendeliome v0.8140 CEP164 Zornitza Stark Mode of inheritance for gene: CEP164 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8139 CEP164 Zornitza Stark reviewed gene: CEP164: Rating: GREEN; Mode of pathogenicity: None; Publications: 34132027, 34013113, 32055034, 27708425, 22863007; Phenotypes: Bardet-Biedl syndrome, Nephronophthisis 15, MIM# 614845, Oro-facio-digital syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8139 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Mendeliome v0.8139 CEP120 Zornitza Stark Phenotypes for gene: CEP120 were changed from to Joubert syndrome 31, MIM# 617761; Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300
Mendeliome v0.8138 CEP120 Zornitza Stark Publications for gene: CEP120 were set to
Mendeliome v0.8137 CEP120 Zornitza Stark Mode of inheritance for gene: CEP120 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8136 CEP120 Zornitza Stark reviewed gene: CEP120: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208211, 33486889, 29847808, 25361962, 27208211; Phenotypes: Joubert syndrome 31, MIM# 617761, Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8136 CEP104 Zornitza Stark Gene: cep104 has been classified as Green List (High Evidence).
Mendeliome v0.8136 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from to Joubert syndrome 25, MIM# 616781; MONDO:0014770
Mendeliome v0.8135 CEP104 Zornitza Stark Publications for gene: CEP104 were set to
Mendeliome v0.8134 CEP104 Zornitza Stark Mode of inheritance for gene: CEP104 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8133 CEP104 Zornitza Stark reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 26477546; Phenotypes: Joubert syndrome 25, MIM# 616781, MONDO:0014770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8133 C5orf42 Zornitza Stark Tag new gene name tag was added to gene: C5orf42.
Mendeliome v0.8133 C5orf42 Zornitza Stark Gene: c5orf42 has been classified as Green List (High Evidence).
Mendeliome v0.8133 C5orf42 Zornitza Stark Phenotypes for gene: C5orf42 were changed from to Joubert syndrome 17, MIM# 614615; Orofaciodigital syndrome VI, MIM# 277170
Mendeliome v0.8132 C5orf42 Zornitza Stark Publications for gene: C5orf42 were set to
Mendeliome v0.8131 C5orf42 Zornitza Stark Mode of inheritance for gene: C5orf42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8130 C5orf42 Zornitza Stark changed review comment from: Well established gene-disease association.

New gene name is CPLANE1.; to: Well established gene-disease associations. More than 10 families reported with each association.

New gene name is CPLANE1.
Mendeliome v0.8130 C5orf42 Zornitza Stark Deleted their comment
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Changed phenotypes: Joubert syndrome 17, MIM# 614615, Orofaciodigital syndrome VI, MIM# 277170
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Changed publications: 22425360, 24178751
Mendeliome v0.8130 C5orf42 Zornitza Stark edited their review of gene: C5orf42: Added comment: Well established gene-disease association.

New gene name is CPLANE1.; Changed publications: 22425360
Mendeliome v0.8130 C21orf2 Zornitza Stark changed review comment from: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.; to: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.

New HGNC approved name is CFAP410.
Mendeliome v0.8130 C21orf2 Zornitza Stark Tag new gene name tag was added to gene: C21orf2.
Mendeliome v0.8130 C21orf2 Zornitza Stark Gene: c21orf2 has been classified as Green List (High Evidence).
Mendeliome v0.8130 C21orf2 Zornitza Stark Phenotypes for gene: C21orf2 were changed from to Spondylometaphyseal dysplasia, axial, MIM# 602271; Retinal dystrophy with macular staphyloma, MIM# 617547
Mendeliome v0.8129 C21orf2 Zornitza Stark Publications for gene: C21orf2 were set to
Mendeliome v0.8128 C21orf2 Zornitza Stark Mode of inheritance for gene: C21orf2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 C21orf2 Zornitza Stark reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26974433, 27548899, 28422394, 26294103, 23105016, 27548899; Phenotypes: Spondylometaphyseal dysplasia, axial, MIM# 602271, Retinal dystrophy with macular staphyloma, MIM# 617547; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 BBS9 Zornitza Stark Gene: bbs9 has been classified as Green List (High Evidence).
Mendeliome v0.8127 BBS9 Zornitza Stark Phenotypes for gene: BBS9 were changed from to Bardet-Biedl syndrome 9, MIM#615986; MONDO:0014437
Mendeliome v0.8126 BBS9 Zornitza Stark Publications for gene: BBS9 were set to
Mendeliome v0.8125 BBS9 Zornitza Stark Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8124 BBS9 Zornitza Stark reviewed gene: BBS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 16380913, 22353939, 32686083, 32037757; Phenotypes: Bardet-Biedl syndrome 9, MIM#615986, MONDO:0014437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8124 BBS7 Zornitza Stark Gene: bbs7 has been classified as Green List (High Evidence).
Mendeliome v0.8124 BBS7 Zornitza Stark Phenotypes for gene: BBS7 were changed from to Bardet-Biedl syndrome 7, MIM# 615984; MONDO:0014435
Mendeliome v0.8123 BBS7 Zornitza Stark Publications for gene: BBS7 were set to
Mendeliome v0.8122 BBS7 Zornitza Stark Mode of inheritance for gene: BBS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8121 BBS7 Zornitza Stark reviewed gene: BBS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12567324, 21937992, 19797195; Phenotypes: Bardet-Biedl syndrome 7, MIM# 615984, MONDO:0014435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8121 BBS5 Zornitza Stark Gene: bbs5 has been classified as Green List (High Evidence).
Mendeliome v0.8121 BBS5 Zornitza Stark Phenotypes for gene: BBS5 were changed from to Bardet-Biedl syndrome 5, MIM#615983; MONDO:0014434
Mendeliome v0.8120 BBS5 Zornitza Stark Publications for gene: BBS5 were set to
Mendeliome v0.8119 BBS5 Zornitza Stark Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8118 BBS5 Zornitza Stark reviewed gene: BBS5: Rating: GREEN; Mode of pathogenicity: None; Publications: 19252258, 15137946, 10053027, 15637713; Phenotypes: Bardet-Biedl syndrome 5, MIM#615983, MONDO:0014434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8118 BBS4 Zornitza Stark Gene: bbs4 has been classified as Green List (High Evidence).
Mendeliome v0.8118 BBS4 Zornitza Stark Phenotypes for gene: BBS4 were changed from to Bardet-Biedl syndrome 4, MIM#615982; MONDO:0014433
Mendeliome v0.8117 BBS4 Zornitza Stark Publications for gene: BBS4 were set to
Mendeliome v0.8116 BBS4 Zornitza Stark Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8115 BBS4 Zornitza Stark reviewed gene: BBS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12016587, 11381270; Phenotypes: Bardet-Biedl syndrome 4, MIM#615982, MONDO:0014433; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8115 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Mendeliome v0.8115 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from to Bardet-Biedl syndrome 3, MIM# 600151; Retinitis pigmentosa 55, MIM# 613575
Mendeliome v0.8114 ARL6 Zornitza Stark Publications for gene: ARL6 were set to
Mendeliome v0.8113 ARL6 Zornitza Stark Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8112 ARL6 Zornitza Stark reviewed gene: ARL6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15258860, 32361989, 31888296, 25402481, 31736247, 19858128; Phenotypes: Bardet-Biedl syndrome 3, MIM# 600151, Retinitis pigmentosa 55, MIM# 613575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8112 IL37 Zornitza Stark Phenotypes for gene: IL37 were changed from Infantile inflammatory bowel disease to Inflammatory bowel disease (infantile ulcerative colitis) 31, MIM# 619398
Mendeliome v0.8111 IL37 Zornitza Stark edited their review of gene: IL37: Changed phenotypes: Inflammatory bowel disease (infantile ulcerative colitis) 31, MIM# 619398
Mendeliome v0.8111 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441
Mendeliome v0.8110 SLCO2A1 Zornitza Stark Publications for gene: SLCO2A1 were set to
Mendeliome v0.8109 SLCO2A1 Zornitza Stark Mode of inheritance for gene: SLCO2A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8108 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495
Mendeliome v0.8108 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23509104, 27134495, 33852188, 22331663, 27134495]; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8108 NDUFB11 Zornitza Stark edited their review of gene: NDUFB11: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8108 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721 to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721; X-linked sideroblastic anaemia
Mendeliome v0.8107 NDUFB11 Zornitza Stark Publications for gene: NDUFB11 were set to 28050600; 27488349; 30423443; 27488349
Mendeliome v0.8106 NDUFB11 Zornitza Stark reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27488349; Phenotypes: X-linked sideroblastic anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8106 PPP2R1A Zornitza Stark changed review comment from: Intellectual disability with variable other features, including CC abnormalities and microcephaly.; to: Intellectual disability with variable other features, including CC abnormalities and microcephaly/macrocephaly.
Mendeliome v0.8106 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Mendeliome v0.8106 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Mendeliome v0.8105 PPP2R1A Zornitza Stark Publications for gene: PPP2R1A were set to
Mendeliome v0.8104 PPP2R1A Zornitza Stark Mode of inheritance for gene: PPP2R1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8103 PPP2R1A Zornitza Stark reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 36, MIM#616362, Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8103 KIF1B Bryony Thompson Classified gene: KIF1B as Amber List (moderate evidence)
Mendeliome v0.8103 KIF1B Bryony Thompson Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Classified gene: ARHGEF10 as Amber List (moderate evidence)
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Added comment: Comment on list classification: ClinGen gene-disease clinical validity classification is limited for this gene.
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8100 PPP2R1A Elena Savva reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26168268, 33106617; Phenotypes: Mental retardation, autosomal dominant 36 MIM#616362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.8100 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Mendeliome v0.8100 CLPB Zornitza Stark Phenotypes for gene: CLPB were changed from to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271
Mendeliome v0.8099 CLPB Zornitza Stark Publications for gene: CLPB were set to
Mendeliome v0.8098 CLPB Zornitza Stark Mode of inheritance for gene: CLPB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8097 CLPB Zornitza Stark reviewed gene: CLPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25597510, 34140661; Phenotypes: 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropaenia, MIM# 616271; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8097 SYK Zornitza Stark Phenotypes for gene: SYK were changed from Immune dysregulation and systemic inflammation to Immunodeficiency-82 with systemic inflammation (IMD82) , MIM#619381
Mendeliome v0.8096 SYK Zornitza Stark reviewed gene: SYK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency-82 with systemic inflammation (IMD82) , MIM#619381; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8096 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8096 PON1 Zornitza Stark Phenotypes for gene: PON1 were changed from to {Coronary artery disease, susceptibility to}
Mendeliome v0.8095 PON1 Zornitza Stark Classified gene: PON1 as Red List (low evidence)
Mendeliome v0.8095 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8094 PON1 Zornitza Stark reviewed gene: PON1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Coronary artery disease, susceptibility to}; Mode of inheritance: None
Mendeliome v0.8094 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8094 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism
Mendeliome v0.8093 ABCB4 Zornitza Stark Publications for gene: ABCB4 were set to
Mendeliome v0.8092 ABCB4 Zornitza Stark Mode of inheritance for gene: ABCB4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8091 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
Mendeliome v0.8091 OAS1 Zornitza Stark Phenotypes for gene: OAS1 were changed from to Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia
Mendeliome v0.8090 OAS1 Zornitza Stark Publications for gene: OAS1 were set to
Mendeliome v0.8089 OAS1 Zornitza Stark Mode of pathogenicity for gene: OAS1 was changed from to Other
Mendeliome v0.8088 OAS1 Zornitza Stark Mode of inheritance for gene: OAS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8087 OAS1 Zornitza Stark reviewed gene: OAS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34145065, 29455859; Phenotypes: Autoinflammatory immunodeficiency, infantile-onset pulmonary alveolar proteinosis, hypogammaglobulinaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8087 SLIT3 Zornitza Stark Marked gene: SLIT3 as ready
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8087 SLIT3 Zornitza Stark Classified gene: SLIT3 as Amber List (moderate evidence)
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8086 SLIT3 Zornitza Stark gene: SLIT3 was added
gene: SLIT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIT3 were set to 33933663
Phenotypes for gene: SLIT3 were set to Congenital diaphragmatic hernia
Review for gene: SLIT3 was set to AMBER
Added comment: Two affected individuals, single family, supportive mouse model.
Sources: Literature
Mendeliome v0.8085 SOCS1 Zornitza Stark Phenotypes for gene: SOCS1 were changed from Common variable immunodeficiency; Early-onset autoimmunity to Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375; Common variable immunodeficiency; Early-onset autoimmunity
Mendeliome v0.8084 SOCS1 Zornitza Stark edited their review of gene: SOCS1: Changed phenotypes: Autoinflammatory syndrome, familial, with or without immunodeficiency, MIM# 619375, Early-onset autoimmunity
Mendeliome v0.8084 LCP2 Zornitza Stark Phenotypes for gene: LCP2 were changed from Severe combined immunodeficiency to Immunodeficiency 81, MIM# 619374; Severe combined immunodeficiency
Mendeliome v0.8083 LCP2 Zornitza Stark edited their review of gene: LCP2: Changed phenotypes: Immunodeficiency 81, MIM# 619374, Severe combined immunodeficiency
Mendeliome v0.8083 IQGAP3 Zornitza Stark Gene: iqgap3 has been classified as Red List (Low Evidence).
Mendeliome v0.8083 IQGAP3 Zornitza Stark gene: IQGAP3 was added
gene: IQGAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQGAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IQGAP3 were set to Hereditary neuropathy
Review for gene: IQGAP3 was set to RED
Added comment: Single multiplex family, intronic variant, limited functional data.
Sources: Literature
Mendeliome v0.8082 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Mendeliome v0.8082 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Mendeliome v0.8082 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from to Dyskeratosis congenita, autosomal dominant 3, MIM# 613990; Revesz syndrome, MIM# 268130
Mendeliome v0.8081 TINF2 Zornitza Stark Publications for gene: TINF2 were set to
Mendeliome v0.8080 TINF2 Zornitza Stark Mode of inheritance for gene: TINF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8079 TINF2 Zornitza Stark edited their review of gene: TINF2: Added comment: RS is a severe variant of DKC with early bone marrow failure and retinopathy. Well established gene-disease associations.; Changed publications: 18252230, 21477109, 18979121, 18669893, 21199492, 33097095; Changed phenotypes: Dyskeratosis congenita, autosomal dominant 3, MIM# 613990, Revesz syndrome, MIM# 268130
Mendeliome v0.8079 POPDC3 Zornitza Stark changed review comment from: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature; to: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Presentation was between adolescence and 40s with proximal muscle weakness primarily affecting the lower limbs, resulting in increased falls and difficulty running. The disorder was slowly progressive, with later involvement of the upper limbs. MRI showed fatty replacement of the thigh muscles and medial gastrocnemius, with some paraspinal muscles also affected. Some patients had calf hypertrophy. Serum CK was markedly elevated.
Sources: Literature
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8079 POPDC3 Zornitza Stark Classified gene: POPDC3 as Green List (high evidence)
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8078 POPDC3 Zornitza Stark gene: POPDC3 was added
gene: POPDC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POPDC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC3 were set to 31610034
Phenotypes for gene: POPDC3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 26, MIM# 618848
Review for gene: POPDC3 was set to GREEN
Added comment: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature
Mendeliome v0.8077 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8077 ACD Zornitza Stark Phenotypes for gene: ACD were changed from to Dyskeratosis congenita, MIM# 616553
Mendeliome v0.8076 ACD Zornitza Stark Publications for gene: ACD were set to
Mendeliome v0.8075 ACD Zornitza Stark Mode of inheritance for gene: ACD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8074 ACD Zornitza Stark Classified gene: ACD as Red List (low evidence)
Mendeliome v0.8074 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8073 ACD Zornitza Stark reviewed gene: ACD: Rating: RED; Mode of pathogenicity: None; Publications: 25205116, 25233904; Phenotypes: Dyskeratosis congenita, MIM# 616553; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8073 USB1 Zornitza Stark Phenotypes for gene: USB1 were changed from Poikiloderma with neutropenia (OMIM #604173) to Poikiloderma with neutropaenia, MIM# 604173; MONDO:0011405
Mendeliome v0.8072 USB1 Zornitza Stark Publications for gene: USB1 were set to 25044170; 27612988
Mendeliome v0.8071 USB1 Zornitza Stark reviewed gene: USB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20004881, 20503306, 34004352, 33624217, 33111394, 32936385, 32620997, 31522452; Phenotypes: Poikiloderma with neutropaenia, MIM# 604173, MONDO:0011405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8071 WRAP53 Zornitza Stark Gene: wrap53 has been classified as Green List (High Evidence).
Mendeliome v0.8071 WRAP53 Zornitza Stark Phenotypes for gene: WRAP53 were changed from to Dyskeratosis congenita, autosomal recessive 3, MIM# 613988
Mendeliome v0.8070 WRAP53 Zornitza Stark Publications for gene: WRAP53 were set to
Mendeliome v0.8069 WRAP53 Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8069 WRAP53 Zornitza Stark Mode of inheritance for gene: WRAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8068 WRAP53 Zornitza Stark reviewed gene: WRAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 21205863, 32303682, 29514627; Phenotypes: Dyskeratosis congenita, autosomal recessive 3, MIM# 613988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8068 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Mendeliome v0.8068 EP300 Zornitza Stark Phenotypes for gene: EP300 were changed from to Rubinstein-Taybi syndrome 2 MIM#613684; Menke-Hennekam syndrome 2 MIM#618333
Mendeliome v0.8067 EP300 Zornitza Stark Publications for gene: EP300 were set to
Mendeliome v0.8066 EP300 Zornitza Stark Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8065 EP300 Elena Savva reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29460469, 24381114; Phenotypes: Rubinstein-Taybi syndrome 2 MIM#613684, Menke-Hennekam syndrome 2 MIM#618333, Colorectal cancer, somatic MIM#114500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.8065 PARN Zornitza Stark Gene: parn has been classified as Green List (High Evidence).
Mendeliome v0.8065 PARN Zornitza Stark Phenotypes for gene: PARN were changed from to Dyskeratosis congenita, autosomal recessive 6, MIM# 616353; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371
Mendeliome v0.8064 PARN Zornitza Stark Publications for gene: PARN were set to
Mendeliome v0.8063 PARN Zornitza Stark Mode of inheritance for gene: PARN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8062 PARN Zornitza Stark reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25893599, 26342108, 25848748; Phenotypes: Dyskeratosis congenita, autosomal recessive 6, MIM# 616353, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8062 KLF1 Zornitza Stark Gene: klf1 has been classified as Green List (High Evidence).
Mendeliome v0.8062 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355
Mendeliome v0.8061 KLF1 Zornitza Stark Publications for gene: KLF1 were set to
Mendeliome v0.8060 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8059 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881; Phenotypes: Dyserythropoietic anaemia, congenital, type IV, MIM# 613673, MONDO:0013355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8059 SPAG17 Zornitza Stark Gene: spag17 has been classified as Red List (Low Evidence).
Mendeliome v0.8059 SPAG17 Zornitza Stark gene: SPAG17 was added
gene: SPAG17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPAG17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG17 were set to 28548327
Phenotypes for gene: SPAG17 were set to Spermatogenic failure 55, MIM#619380
Review for gene: SPAG17 was set to RED
Added comment: Single family reported with two affected brothers, homozygous missense variant.
Sources: Literature
Mendeliome v0.8058 CATIP Zornitza Stark Marked gene: CATIP as ready
Mendeliome v0.8058 CATIP Zornitza Stark Gene: catip has been classified as Red List (Low Evidence).
Mendeliome v0.8058 CATIP Zornitza Stark gene: CATIP was added
gene: CATIP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CATIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CATIP were set to 32503832
Phenotypes for gene: CATIP were set to Spermatogenic failure 54, MIM# 619379
Review for gene: CATIP was set to RED
Added comment: Homozygous missense variant reported in a single consanguineous family with 4 affecteds. Limited functional data.
Sources: Expert list
Mendeliome v0.8057 NCDN Zornitza Stark Phenotypes for gene: NCDN were changed from neurodevelopmental delay, intellectual disability, and epilepsy to Neurodevelopmental disorder with infantile epileptic spasms (NEDIES), MIM#619373
Mendeliome v0.8056 NCDN Zornitza Stark reviewed gene: NCDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with infantile epileptic spasms (NEDIES), MIM#619373; Mode of inheritance: None
Mendeliome v0.8056 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Mendeliome v0.8056 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Mendeliome v0.8055 HAX1 Zornitza Stark Publications for gene: HAX1 were set to
Mendeliome v0.8054 HAX1 Zornitza Stark Mode of inheritance for gene: HAX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8053 HAX1 Zornitza Stark reviewed gene: HAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17187068, 18611981, 19036076; Phenotypes: Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738, Kostmann syndrome MONDO:0012548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8053 NFS1 Zornitza Stark Phenotypes for gene: NFS1 were changed from Complex II/III deficiency; multisystem organ failure to Combined oxidative phosphorylation deficiency 52, MIM#619386; Complex II/III deficiency; multisystem organ failure
Mendeliome v0.8052 NFS1 Zornitza Stark Publications for gene: NFS1 were set to 24498631
Mendeliome v0.8051 NFS1 Zornitza Stark edited their review of gene: NFS1: Changed phenotypes: Combined oxidative phosphorylation deficiency 52, MIM#619386, Complex II/III deficiency, multisystem organ failure
Mendeliome v0.8051 DNAJC30 Zornitza Stark Phenotypes for gene: DNAJC30 were changed from Leber Hereditary Optic Neuropathy to Leber Hereditary Optic Neuropathy, MIM#619382
Mendeliome v0.8050 DNAJC30 Zornitza Stark edited their review of gene: DNAJC30: Changed phenotypes: Leber Hereditary Optic Neuropathy, MIM#619382
Mendeliome v0.8050 MYL9 Zornitza Stark Phenotypes for gene: MYL9 were changed from Megacystis-microcolon-intestinal hypoperistalsis syndrome to Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8049 MYL9 Zornitza Stark edited their review of gene: MYL9: Changed phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8049 ARCN1 Zornitza Stark Phenotypes for gene: ARCN1 were changed from to Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164)
Mendeliome v0.8048 ARCN1 Zornitza Stark Publications for gene: ARCN1 were set to
Mendeliome v0.8047 ARCN1 Zornitza Stark Mode of inheritance for gene: ARCN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8046 ARCN1 Zornitza Stark reviewed gene: ARCN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476655, 33154040; Phenotypes: Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (MIM#617164); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8046 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Mendeliome v0.8046 NBEAL2 Zornitza Stark Phenotypes for gene: NBEAL2 were changed from to Gray platelet syndrome, MIM# 139090
Mendeliome v0.8045 NBEAL2 Zornitza Stark Publications for gene: NBEAL2 were set to
Mendeliome v0.8044 NBEAL2 Zornitza Stark Mode of inheritance for gene: NBEAL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8043 NBEAL2 Zornitza Stark reviewed gene: NBEAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21765412, 21765411, 21765413; Phenotypes: Gray platelet syndrome, MIM# 139090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8043 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
Mendeliome v0.8043 GFI1 Zornitza Stark Phenotypes for gene: GFI1 were changed from to Neutropaenia, severe congenital 2, autosomal dominant, MIM# 613107
Mendeliome v0.8042 GFI1 Zornitza Stark Publications for gene: GFI1 were set to
Mendeliome v0.8041 GFI1 Zornitza Stark Mode of inheritance for gene: GFI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8040 GFI1 Zornitza Stark reviewed gene: GFI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12778173, 20560965, 11810106, 22684987; Phenotypes: Neutropaenia, severe congenital 2, autosomal dominant, MIM# 613107; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8040 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Green List (High Evidence).
Mendeliome v0.8040 SLC13A5 Zornitza Stark Phenotypes for gene: SLC13A5 were changed from to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392
Mendeliome v0.8039 SLC13A5 Zornitza Stark Publications for gene: SLC13A5 were set to
Mendeliome v0.8038 SLC13A5 Zornitza Stark Mode of inheritance for gene: SLC13A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8037 SLC13A5 Zornitza Stark reviewed gene: SLC13A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24995870, 26384929; Phenotypes: Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905, MONDO:0014392; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8037 GATA2 Zornitza Stark Marked gene: GATA2 as ready
Mendeliome v0.8037 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Mendeliome v0.8037 GATA2 Zornitza Stark Phenotypes for gene: GATA2 were changed from to Immunodeficiency 21, MIM# 614172; GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982; Emberger syndrome, MIM# 614038; Deafness-lymphoedema-leukaemia syndrome MONDO:0013540
Mendeliome v0.8036 GATA2 Zornitza Stark Publications for gene: GATA2 were set to
Mendeliome v0.8035 GATA2 Zornitza Stark Mode of inheritance for gene: GATA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8034 GATA2 Zornitza Stark reviewed gene: GATA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21670465, 21242295, 21892158; Phenotypes: Immunodeficiency 21, MIM# 614172, GATA2 deficiency with susceptibility to MDS/AML MONDO:0042982, Emberger syndrome, MIM# 614038, Deafness-lymphoedema-leukaemia syndrome MONDO:0013540; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8034 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Mendeliome v0.8034 GATA1 Zornitza Stark Gene: gata1 has been classified as Green List (High Evidence).
Mendeliome v0.8034 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367
Mendeliome v0.8033 GATA1 Zornitza Stark Mode of inheritance for gene: GATA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8032 GATA1 Zornitza Stark reviewed gene: GATA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.8032 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
Mendeliome v0.8032 ELANE Zornitza Stark Phenotypes for gene: ELANE were changed from to Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700
Mendeliome v0.8031 ELANE Zornitza Stark Publications for gene: ELANE were set to
Mendeliome v0.8030 ELANE Zornitza Stark Mode of inheritance for gene: ELANE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8029 ELANE Zornitza Stark reviewed gene: ELANE: Rating: GREEN; Mode of pathogenicity: None; Publications: 19036076; Phenotypes: Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8029 EFL1 Zornitza Stark Gene: efl1 has been classified as Green List (High Evidence).
Mendeliome v0.8029 EFL1 Zornitza Stark Phenotypes for gene: EFL1 were changed from to Shwachman-Diamond syndrome 2, MIM# 617941
Mendeliome v0.8028 EFL1 Zornitza Stark Publications for gene: EFL1 were set to
Mendeliome v0.8027 EFL1 Zornitza Stark Mode of inheritance for gene: EFL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8026 EFL1 Zornitza Stark reviewed gene: EFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28331068, 31151987; Phenotypes: Shwachman-Diamond syndrome 2, MIM# 617941; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8026 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
Mendeliome v0.8026 CXCR4 Zornitza Stark Phenotypes for gene: CXCR4 were changed from to WHIM syndrome, MIM# 193670
Mendeliome v0.8025 CXCR4 Zornitza Stark Publications for gene: CXCR4 were set to
Mendeliome v0.8024 CXCR4 Zornitza Stark Mode of inheritance for gene: CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8023 CXCR4 Zornitza Stark reviewed gene: CXCR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12692554; Phenotypes: WHIM syndrome, MIM# 193670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8023 CTC1 Zornitza Stark Marked gene: CTC1 as ready
Mendeliome v0.8023 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Mendeliome v0.8023 CTC1 Zornitza Stark Phenotypes for gene: CTC1 were changed from to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Mendeliome v0.8022 CTC1 Zornitza Stark Publications for gene: CTC1 were set to
Mendeliome v0.8021 CTC1 Zornitza Stark Mode of inheritance for gene: CTC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8020 CTC1 Zornitza Stark reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22267198, 22387016; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8020 ANKRD26 Zornitza Stark Gene: ankrd26 has been classified as Green List (High Evidence).
Mendeliome v0.8020 ANKRD26 Zornitza Stark Phenotypes for gene: ANKRD26 were changed from to Thrombocytopaenia 2, MIM# 188000
Mendeliome v0.8019 ANKRD26 Zornitza Stark Publications for gene: ANKRD26 were set to
Mendeliome v0.8018 ANKRD26 Zornitza Stark Mode of inheritance for gene: ANKRD26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8017 ANKRD26 Zornitza Stark Tag 5'UTR tag was added to gene: ANKRD26.
Mendeliome v0.8017 ANKRD26 Zornitza Stark reviewed gene: ANKRD26: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211618; Phenotypes: Thrombocytopaenia 2, MIM# 188000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8017 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Mendeliome v0.8017 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from to Reticular dysgenesis, MIM# 267500
Mendeliome v0.8016 AK2 Zornitza Stark Publications for gene: AK2 were set to
Mendeliome v0.8015 AK2 Zornitza Stark Mode of inheritance for gene: AK2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8014 AK2 Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416; Phenotypes: Reticular dysgenesis, MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8014 ADA2 Zornitza Stark Gene: ada2 has been classified as Green List (High Evidence).
Mendeliome v0.8014 ADA2 Zornitza Stark Phenotypes for gene: ADA2 were changed from to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688
Mendeliome v0.8013 ADA2 Zornitza Stark Publications for gene: ADA2 were set to
Mendeliome v0.8012 ADA2 Zornitza Stark Mode of inheritance for gene: ADA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8011 ADA2 Zornitza Stark commented on gene: ADA2: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome (VAIHS) is an autosomal recessive multisystem disorder with onset in childhood. The phenotype is highly variable, but most patients have features of a systemic vascular inflammatory disorder with skin ulceration and recurrent strokes affecting the small vessels of the brain resulting in neurologic dysfunction. Other features may include recurrent fever, elevated acute-phase proteins, myalgias, lesions resembling polyarteritis nodosa, and/or livedo racemosa or reticularis with an inflammatory vasculitis on biopsy. Some patients may have renal and/or gastrointestinal involvement, hypertension, aneurysms, or ischemic necrosis of the digits. Some affected individuals have immunodeficiency. At least 10 unrelated families reported, the p.Gly47Arg variant is a common founder variant in the Jewish population.
Mendeliome v0.8011 ADA2 Zornitza Stark reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24552284, 24552285, 33791889; Phenotypes: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8011 IFT74 Zornitza Stark Phenotypes for gene: IFT74 were changed from Bardet-Biedl syndrome 20, MIM# 617119 to Bardet-Biedl syndrome 20, MIM# 617119; Joubert syndrome
Mendeliome v0.8010 IFT74 Zornitza Stark Publications for gene: IFT74 were set to 27486776; 32144365
Mendeliome v0.8009 IFT74 Zornitza Stark edited their review of gene: IFT74: Added comment: PMID 33531668: Identified IFT74 as a JBTS-associated gene in 3 unrelated families through WES. All the affected individuals carried truncated variants and shared one missense variant (p.Q179E) found only in East Asians. The expression of the human p.Q179E-IFT74 variant displayed compromised rescue effects in zebrafish ift74 morphants. Attenuated ciliogenesis; altered distribution of IFT proteins and ciliary membrane proteins, including ARL13B, INPP5E, and GPR161; and disrupted hedgehog signaling were observed in patient fibroblasts with IFT74 variants.; Changed publications: 27486776, 32144365, 33531668; Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 617119, Joubert syndrome
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8009 RFX4 Zornitza Stark Classified gene: RFX4 as Green List (high evidence)
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8008 RFX4 Zornitza Stark gene: RFX4 was added
gene: RFX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX4 were set to 33658631
Phenotypes for gene: RFX4 were set to ID, ASD, ADHD
Review for gene: RFX4 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8007 RFX3 Zornitza Stark Classified gene: RFX3 as Green List (high evidence)
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8006 RFX3 Zornitza Stark gene: RFX3 was added
gene: RFX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX3 were set to 33658631
Phenotypes for gene: RFX3 were set to ID, ASD, ADHD
Review for gene: RFX3 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8005 RFX7 Zornitza Stark Classified gene: RFX7 as Green List (high evidence)
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8004 RFX7 Zornitza Stark gene: RFX7 was added
gene: RFX7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX7 were set to 33658631
Phenotypes for gene: RFX7 were set to ID, ASD, ADHD
Review for gene: RFX7 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8003 SEMA3F Zornitza Stark Classified gene: SEMA3F as Green List (high evidence)
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8002 SEMA3F Zornitza Stark gene: SEMA3F was added
gene: SEMA3F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA3F were set to 33495532
Phenotypes for gene: SEMA3F were set to Hypogonadotropic hypogonadism
Review for gene: SEMA3F was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 10 individuals from 7 families with heterozygous SEMA3F missense variants. In 4 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Provide unequivocal human embryonic data showing the expression of SEMA3F along the developing human GnRH migratory pathway. SEMA3Fs harboring the P452T, T29M, and T724M missense variants showed impaired SEMA3F secretion in whole cell lysates.
Sources: Literature
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8001 PLXNA3 Zornitza Stark Classified gene: PLXNA3 as Green List (high evidence)
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8000 PLXNA3 Zornitza Stark gene: PLXNA3 was added
gene: PLXNA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLXNA3 were set to 33495532
Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism
Review for gene: PLXNA3 was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants. In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3.
Sources: Literature
Mendeliome v0.7999 DLG4 Zornitza Stark Phenotypes for gene: DLG4 were changed from Intellectual disability; Marfanoid habitus to Intellectual developmental disorder 62, MIM# 618793
Mendeliome v0.7998 DLG4 Zornitza Stark Publications for gene: DLG4 were set to 27479843; 25123844; 19617690; 29460436; 23020937; 28135719
Mendeliome v0.7997 DLG4 Zornitza Stark edited their review of gene: DLG4: Added comment: PMID 33597769: 53 patients (42 previously unpublished) with DLG4 variants. The clinical picture predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder.; Changed publications: 27479843, 25123844, 19617690, 29460436, 23020937, 28135719, 33597769; Changed phenotypes: Intellectual developmental disorder 62, MIM# 618793
Mendeliome v0.7997 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Mendeliome v0.7997 GNAI1 Zornitza Stark Phenotypes for gene: GNAI1 were changed from to Intellectual disability; seizures; hypotonia
Mendeliome v0.7996 GNAI1 Zornitza Stark Publications for gene: GNAI1 were set to
Mendeliome v0.7995 GNAI1 Zornitza Stark Mode of inheritance for gene: GNAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7994 GNAI1 Zornitza Stark reviewed gene: GNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 33473207; Phenotypes: Intellectual disability, seizures, hypotonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7994 SURF1 Elena Savva reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24027061; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7994 FARSA Zornitza Stark Classified gene: FARSA as Green List (high evidence)
Mendeliome v0.7994 FARSA Zornitza Stark Gene: farsa has been classified as Green List (High Evidence).
Mendeliome v0.7993 FARSA Zornitza Stark edited their review of gene: FARSA: Added comment: Schuch et al. (2021) report 3 unrelated individuals with bi-allelic variants in FARSA. Identified through WES and variants segregated with disease. Functional evidence was obtained with reduced FARS1 enzyme activity levels in fibroblasts or EBV-transformed lymphoblastoid cell lines (EBV-LCLs) of patients. Common to all was a chronic interstitial lung disease starting early in life and characterized by bilateral ground-glass opacification on HR-CT, and cholesterol pneumonitis in lung histology. Additional abnormalities in other organ systems include liver disease, neurological manifestations, and growth restriction.; Changed rating: GREEN; Changed publications: 31355908, 33598926; Changed phenotypes: Rajab interstitial lung disease with brain calcifications 2, MIM# 619013
Mendeliome v0.7993 LAMA5 Bryony Thompson Phenotypes for gene: LAMA5 were changed from to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Mendeliome v0.7992 LAMA5 Bryony Thompson Publications for gene: LAMA5 were set to
Mendeliome v0.7991 LAMA5 Bryony Thompson Mode of inheritance for gene: LAMA5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7990 LAMA5 Bryony Thompson reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 33242826, 29534211, 16790509, 30589377, 28735299, 30631761; Phenotypes: bent bone dysplasia, nephrotic syndrome, Presynaptic congenital myasthenic syndrome, multisystem syndrome, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7990 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7990 ZNF81 Zornitza Stark Phenotypes for gene: ZNF81 were changed from to Intellectual disability
Mendeliome v0.7989 ZNF81 Zornitza Stark Publications for gene: ZNF81 were set to
Mendeliome v0.7988 ZNF81 Zornitza Stark Mode of inheritance for gene: ZNF81 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7987 ZNF81 Zornitza Stark Classified gene: ZNF81 as Red List (low evidence)
Mendeliome v0.7987 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7986 ZNF81 Zornitza Stark reviewed gene: ZNF81: Rating: RED; Mode of pathogenicity: None; Publications: 15121780; Phenotypes: Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7986 RELN Ee Ming Wong edited their review of gene: RELN: Added comment: - Six affected individuals carrying missense variants in RELN including
1. Two individuals with compound heterozygous variants
- One of the variants has 26 homozygotes in gnomAD and therefore pathogenicity of this variant is in question
- LoF demonstrated for three of the variants (reduced RELN secretion), except for p.Y1821H which demonstrated an apparently increased RELN secretion (GoF)
2. Two brothers carrying the maternally inherited variant (mother apparently healthy)
- LoF demonstrated for these variants
3. Two individuals de novo for RELN variants
- Dominant negative demonstrated for these variants where secretion of WT-RELN was impaired when co-transfected with mutant constructs in HEK293T cells; Changed rating: AMBER; Changed publications: Riva et al bioRxiv (pre-print, not peer-reviewed); Changed phenotypes: Pachygyria, Polymicrogyria, Heterotopia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7986 NIID Bryony Thompson Marked STR: NIID as ready
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7986 NIID Bryony Thompson Classified STR: NIID as Green List (high evidence)
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7985 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[(66_517)]
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 7-60
Pathogenic repeat range: >=61-500
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Classified gene: NOTCH2NL as No list
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Added comment: Comment on list classification: STR is the only reported cause of disease for this gene. It has been added as an STR under NIID.
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Gene: notch2nl has been removed from the panel.
Mendeliome v0.7983 TRPM6 Zornitza Stark Marked gene: TRPM6 as ready
Mendeliome v0.7983 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
Mendeliome v0.7983 TRPM6 Zornitza Stark Phenotypes for gene: TRPM6 were changed from to Hypomagnesaemia 1, intestinal (MIM#602014)
Mendeliome v0.7982 TRPM6 Zornitza Stark Mode of inheritance for gene: TRPM6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Phenotypes for gene: CNTNAP1 were changed from to Hypomyelinating neuropathy, congenital, 3, MIM#618186; Lethal congenital contracture syndrome 7, MIM# 616286
Mendeliome v0.7980 CNTNAP1 Zornitza Stark Publications for gene: CNTNAP1 were set to
Mendeliome v0.7979 CNTNAP1 Zornitza Stark Mode of inheritance for gene: CNTNAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7978 CNTNAP1 Zornitza Stark reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28374019, 29511323, 27668699; Phenotypes: Hypomyelinating neuropathy, congenital, 3, MIM#618186, Lethal congenital contracture syndrome 7, MIM# 616286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7978 GLDN Zornitza Stark Gene: gldn has been classified as Green List (High Evidence).
Mendeliome v0.7978 GLDN Zornitza Stark Phenotypes for gene: GLDN were changed from to Lethal congenital contracture syndrome 11, MIM# 617194; MONDO:0014965
Mendeliome v0.7977 GLDN Zornitza Stark Publications for gene: GLDN were set to
Mendeliome v0.7976 GLDN Zornitza Stark Mode of inheritance for gene: GLDN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7975 GLDN Zornitza Stark reviewed gene: GLDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616481, 32812332, 28726266; Phenotypes: Lethal congenital contracture syndrome 11, MIM# 617194, MONDO:0014965; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7975 ZBTB42 Zornitza Stark Marked gene: ZBTB42 as ready
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7975 ZBTB42 Zornitza Stark Classified gene: ZBTB42 as Amber List (moderate evidence)
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7974 ZBTB42 Zornitza Stark gene: ZBTB42 was added
gene: ZBTB42 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB42 were set to 25055871
Phenotypes for gene: ZBTB42 were set to Lethal congenital contracture syndrome 6, MIM# 616248
Review for gene: ZBTB42 was set to AMBER
Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model.
Sources: Expert Review
Mendeliome v0.7973 MYBPC1 Zornitza Stark Gene: mybpc1 has been classified as Green List (High Evidence).
Mendeliome v0.7973 MYBPC1 Zornitza Stark Phenotypes for gene: MYBPC1 were changed from to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4, MIM# 614915; Myopathy, congenital, with tremor MIM#618524
Mendeliome v0.7972 MYBPC1 Zornitza Stark Publications for gene: MYBPC1 were set to
Mendeliome v0.7971 MYBPC1 Zornitza Stark Mode of inheritance for gene: MYBPC1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7970 MYBPC1 Zornitza Stark reviewed gene: MYBPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20045868, 22610851, 23873045, 26661508, 31264822, 31025394; Phenotypes: Arthrogryposis, distal, type 1B 614335, Lethal congenital contracture syndrome 4, MIM# 614915, Myopathy, congenital, with tremor MIM#618524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7970 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Mendeliome v0.7970 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598 to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis
Mendeliome v0.7969 ERBB3 Zornitza Stark Publications for gene: ERBB3 were set to 17701904; 31752936
Mendeliome v0.7968 ADCY6 Zornitza Stark Phenotypes for gene: ADCY6 were changed from Lethal congenital contracture syndrome 8, OMIM # 616287 to Lethal congenital contracture syndrome 8, OMIM # 616287; MONDO:0014570
Mendeliome v0.7967 ADGRG6 Zornitza Stark edited their review of gene: ADGRG6: Changed phenotypes: Lethal congenital contracture syndrome 9, MIM #616503, MONDO:0014670
Mendeliome v0.7967 TRPM6 Kristin Rigbye reviewed gene: TRPM6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomagnesemia 1, intestinal (MIM#602014), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7967 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Mendeliome v0.7967 MUSK Zornitza Stark Phenotypes for gene: MUSK were changed from to Fetal akinesia deformation sequence 1, MIM# 208150; MONDO:0100101; Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325; MONDO:0014587
Mendeliome v0.7966 MUSK Zornitza Stark Publications for gene: MUSK were set to
Mendeliome v0.7965 MUSK Zornitza Stark Mode of inheritance for gene: MUSK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7964 MUSK Zornitza Stark reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25537362, 25612909, 8653786, 31750350, 15496425, 19949040, 20371544, 32253145; Phenotypes: Fetal akinesia deformation sequence 1, MIM# 208150, MONDO:0100101, Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325, MONDO:0014587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7964 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Mendeliome v0.7964 DOK7 Zornitza Stark Phenotypes for gene: DOK7 were changed from to Myasthenic syndrome, congenital, 10, MIM# 254300; Fetal akinesia deformation sequence 3, MIM# 618389
Mendeliome v0.7963 DOK7 Zornitza Stark Publications for gene: DOK7 were set to
Mendeliome v0.7962 DOK7 Zornitza Stark Mode of inheritance for gene: DOK7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7961 DOK7 Zornitza Stark reviewed gene: DOK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16917026, 18626973, 20147321, 16794080, 31453852, 29395672, 32360404, 19261599, 31880392; Phenotypes: Myasthenic syndrome, congenital, 10, MIM# 254300, Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7961 TPM2 Zornitza Stark Marked gene: TPM2 as ready
Mendeliome v0.7961 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Mendeliome v0.7961 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from to Arthrogryposis, distal, type 1A 108120; Arthrogryposis, distal, type 2B4 108120; CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Multiple pterygium syndrome
Mendeliome v0.7960 TPM2 Zornitza Stark Publications for gene: TPM2 were set to
Mendeliome v0.7959 TPM2 Zornitza Stark Mode of inheritance for gene: TPM2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7958 TPM2 Zornitza Stark reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32092148, 27726070, 32092148, 24692096; Phenotypes: Arthrogryposis, distal, type 1A 108120, Arthrogryposis, distal, type 2B4 108120, CAP myopathy 2 609285, Nemaline myopathy 4, autosomal dominant 609285, Multiple pterygium syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7958 CHRNG Zornitza Stark Gene: chrng has been classified as Green List (High Evidence).
Mendeliome v0.7958 CHRNG Zornitza Stark Phenotypes for gene: CHRNG were changed from to Escobar syndrome, MIM# 265000; Multiple pterygium syndrome, lethal type, MIM# 253290; MONDO:0009926; MONDO:0009668
Mendeliome v0.7957 CHRNG Zornitza Stark Publications for gene: CHRNG were set to
Mendeliome v0.7956 CHRNG Zornitza Stark Mode of inheritance for gene: CHRNG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7955 CHRNG Zornitza Stark reviewed gene: CHRNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16826520, 16826531, 22167768; Phenotypes: Escobar syndrome, MIM# 265000, Multiple pterygium syndrome, lethal type, MIM# 253290, MONDO:0009926, MONDO:0009668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7955 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7955 CD207 Zornitza Stark Phenotypes for gene: CD207 were changed from to Birbeck granule deficiency, MIM# 613393
Mendeliome v0.7954 CD207 Zornitza Stark Publications for gene: CD207 were set to
Mendeliome v0.7953 CD207 Zornitza Stark Mode of inheritance for gene: CD207 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7952 CD207 Zornitza Stark Classified gene: CD207 as Red List (low evidence)
Mendeliome v0.7952 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 CD207 Zornitza Stark reviewed gene: CD207: Rating: RED; Mode of pathogenicity: None; Publications: 15816828; Phenotypes: Birbeck granule deficiency, MIM# 613393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7951 KIF17 Zornitza Stark Gene: kif17 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 KIF17 Zornitza Stark gene: KIF17 was added
gene: KIF17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF17 were set to 33922911; 30458707; 28341548
Phenotypes for gene: KIF17 were set to Microphthalmia; Coloboma
Review for gene: KIF17 was set to RED
Added comment: Two siblings reported with MAC spectrum and homozygous missense variant in this gene. Some pre-existing data linking KIF17 to eye development.
Sources: Literature
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7950 SASH3 Zornitza Stark Classified gene: SASH3 as Green List (high evidence)
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7949 SASH3 Zornitza Stark gene: SASH3 was added
gene: SASH3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SASH3 were set to 33876203
Phenotypes for gene: SASH3 were set to Combined immunodeficiency; immune dysregulation
Review for gene: SASH3 was set to GREEN
Added comment: Four unrelated males reported presenting with combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopaenias. One missense variant, rest were nonsense.
Sources: Literature
Mendeliome v0.7948 FOXP1 Zornitza Stark Publications for gene: FOXP1 were set to
Mendeliome v0.7947 FOXP1 Zornitza Stark Mode of inheritance for gene: FOXP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7946 FOXP1 Zornitza Stark changed review comment from: At least 5 unrelated individuals reported.; to: At least 30 unrelated individuals reported.
Mendeliome v0.7946 FOXP1 Zornitza Stark edited their review of gene: FOXP1: Changed publications: 26633542, 28741757, 34109629
Mendeliome v0.7946 FOXP1 Zornitza Stark reviewed gene: FOXP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26633542, 28741757; Phenotypes: Mental retardation with language impairment and with or without autistic features 613670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7946 PARP6 Zornitza Stark Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Mendeliome v0.7945 PARP6 Zornitza Stark edited their review of gene: PARP6: Changed publications: 34067418
Mendeliome v0.7945 DNAH2 Zornitza Stark edited their review of gene: DNAH2: Added comment: PMID 32732226: compound het variants identified in a fetus with hydrops and complex congenital heart disease detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, heterotaxy, complex congenital heart disease, hypotrophic splenium, and common mesentery.; Changed publications: 30811583, 32732226; Changed phenotypes: Spermatogenic failure 45, MIM# 619094, Heterotaxy
Mendeliome v0.7945 MYBPC2 Zornitza Stark Gene: mybpc2 has been classified as Red List (Low Evidence).
Mendeliome v0.7945 MYBPC2 Zornitza Stark gene: MYBPC2 was added
gene: MYBPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC2 were set to 32732226
Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium
Review for gene: MYBPC2 was set to RED
Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs.
Sources: Literature
Mendeliome v0.7944 SCN7A Zornitza Stark Gene: scn7a has been classified as Red List (Low Evidence).
Mendeliome v0.7944 SCN7A Zornitza Stark gene: SCN7A was added
gene: SCN7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCN7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN7A were set to 32732226
Phenotypes for gene: SCN7A were set to Holoprosencephaly
Review for gene: SCN7A was set to RED
Added comment: Novel candidate gene identified in a fetus with holoprosencephaly detected by ultrasound. Autopsy showed multiple congenital abnormalities including IUGR, microcephaly, bilateral, ablepharon, corpus callosum agenesis, myelomeningocele, tracheal atresia, absent nipples, unilateral simian crease, and hypoplastic phalanges. Compound heterozygous variants including a truncating variant were found by exome sequencing with concordant segregation.
Sources: Literature
Mendeliome v0.7943 SPTBN5 Zornitza Stark Marked gene: SPTBN5 as ready
Mendeliome v0.7943 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Mendeliome v0.7943 SPTBN5 Zornitza Stark gene: SPTBN5 was added
gene: SPTBN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN5 were set to 32732226; 28007035
Phenotypes for gene: SPTBN5 were set to Sacral agenesis; congenital anomalies
Review for gene: SPTBN5 was set to RED
Added comment: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v0.7942 WDR91 Zornitza Stark Phenotypes for gene: WDR91 were changed from to Hydrocephalus; cerebellar hypoplasia; hygroma
Mendeliome v0.7941 WDR91 Zornitza Stark Publications for gene: WDR91 were set to
Mendeliome v0.7940 WDR91 Zornitza Stark Mode of inheritance for gene: WDR91 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7939 WDR91 Zornitza Stark Classified gene: WDR91 as Amber List (moderate evidence)
Mendeliome v0.7939 WDR91 Zornitza Stark Gene: wdr91 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7938 WDR91 Zornitza Stark commented on gene: WDR91: PMID 32732226: Novel candidate gene identified in a fetus with hygroma and hydrocephaly detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma, macrocephaly, abnormal ears, unilateral simian crease, hydrocephaly, cerebellar hypoplasia, and interventricular communication. A homozygous truncating variant was found by exome sequencing with concordant segregation among 4 affected fetus, 2 healthy sibs and both parents. Mouse models support role in brain development.
Mendeliome v0.7938 WDR91 Zornitza Stark reviewed gene: WDR91: Rating: AMBER; Mode of pathogenicity: None; Publications: 34028500, 28860274, 32732226; Phenotypes: Hydrocephalus, cerebellar hypoplasia, hygroma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7938 PLEKHN1 Zornitza Stark Gene: plekhn1 has been classified as Red List (Low Evidence).
Mendeliome v0.7938 PLEKHN1 Zornitza Stark gene: PLEKHN1 was added
gene: PLEKHN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHN1 were set to 33884296
Phenotypes for gene: PLEKHN1 were set to Sensory Neuropathy
Review for gene: PLEKHN1 was set to RED
Added comment: Hom missense variant in single patient with severely reduced/absent pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark Gene: znf3 has been classified as Red List (Low Evidence).
Mendeliome v0.7937 SMPDL3A Seb Lunke changed review comment from: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature; to: Hom missense variant in twin sisters with severely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark gene: ZNF3 was added
gene: ZNF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF3 were set to 32732226
Phenotypes for gene: ZNF3 were set to Hydrocephalus; cleft palate; microphthalmia
Review for gene: ZNF3 was set to RED
Added comment: Novel candidate gene identified in a fetus with hydrocephaly and facial cleft detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including a median cleft palate, partial maxillar agenesis, bilateral severe microphthalmia, arhinencephaly, partial thalamic fusion. A homozygous truncating variant (c.396A>G/ p.*132Trpext*69) in ZNF3 was found by exome sequencing.
Sources: Literature
Mendeliome v0.7936 SMPDL3A Seb Lunke Gene: smpdl3a has been classified as Red List (Low Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Classified gene: WRAP73 as Amber List (moderate evidence)
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 SMPDL3A Seb Lunke gene: SMPDL3A was added
gene: SMPDL3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMPDL3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPDL3A were set to 33884296
Phenotypes for gene: SMPDL3A were set to Sensory Neuropathy
Added comment: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7935 WRAP73 Zornitza Stark gene: WRAP73 was added
gene: WRAP73 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WRAP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WRAP73 were set to 33693649
Phenotypes for gene: WRAP73 were set to Microsperophakia
Review for gene: WRAP73 was set to AMBER
Added comment: Two Indian families with same homozygous missense, (p.Pro383Leu) and supportive functional data (zebrafish model).
Sources: Literature
Mendeliome v0.7934 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; Dystonia
Mendeliome v0.7933 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Changed publications: 33236446, 33866603
Mendeliome v0.7933 EIF2AK2 Zornitza Stark Publications for gene: EIF2AK2 were set to 32197074
Mendeliome v0.7932 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Added comment: Four unrelated families reported with dystonia, recurrent variant, (p.Gly130Arg); Changed publications: 32197074, 33866603; Changed phenotypes: Intellectual disability, white matter abnormalities, ataxia, regression with febrile illness, Dystonia
Mendeliome v0.7932 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Green List (High Evidence).
Mendeliome v0.7932 SLC37A4 Zornitza Stark Phenotypes for gene: SLC37A4 were changed from to Glycogen storage disease Ib 232220; Glycogen storage disease Ic 232240; Congenital disorder of glycosylation
Mendeliome v0.7931 SLC37A4 Zornitza Stark Publications for gene: SLC37A4 were set to
Mendeliome v0.7930 SLC37A4 Zornitza Stark Mode of inheritance for gene: SLC37A4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7929 SLC37A4 Zornitza Stark reviewed gene: SLC37A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33964207, 9675154, 9758626; Phenotypes: Glycogen storage disease Ib 232220, Glycogen storage disease Ic 232240, Congenital disorder of glycosylation; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7929 TUBA1A Zornitza Stark Marked gene: TUBA1A as ready
Mendeliome v0.7929 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Mendeliome v0.7929 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603; Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7928 TUBA1A Zornitza Stark Publications for gene: TUBA1A were set to
Mendeliome v0.7927 TUBA1A Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7926 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7926 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome; Deafness to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v0.7925 COL9A3 Zornitza Stark Publications for gene: COL9A3 were set to 30450842; 31090205; 24273071; 10090888; 15551337; 33078831; 15917166
Mendeliome v0.7924 BCAS3 Zornitza Stark Phenotypes for gene: BCAS3 were changed from to Syndromic neurodevelopmental disorder
Mendeliome v0.7923 BCAS3 Zornitza Stark Publications for gene: BCAS3 were set to
Mendeliome v0.7922 BCAS3 Zornitza Stark Mode of inheritance for gene: BCAS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Marked gene: ANGPTL8 as ready
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Classified gene: ANGPTL8 as Red List (low evidence)
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7920 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v0.7920 SRCAP Zornitza Stark Phenotypes for gene: SRCAP were changed from to Floating-Harbor syndrome MIM#136140; Neurodevelopmental disorder, non-Floating Harbor
Mendeliome v0.7919 SRCAP Zornitza Stark Publications for gene: SRCAP were set to
Mendeliome v0.7918 SRCAP Zornitza Stark Mode of inheritance for gene: SRCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7917 SRCAP Zornitza Stark reviewed gene: SRCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33909990; Phenotypes: Floating-Harbor syndrome MIM#136140, Neurodevelopmental disorder, non-Floating Harbor; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Marked gene: ADAMTSL2 as ready
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Gene: adamtsl2 has been classified as Green List (High Evidence).
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from to Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome
Mendeliome v0.7916 ADAMTSL2 Zornitza Stark Publications for gene: ADAMTSL2 were set to
Mendeliome v0.7915 ADAMTSL2 Zornitza Stark Mode of inheritance for gene: ADAMTSL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7914 ADAMTSL2 Zornitza Stark reviewed gene: ADAMTSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33369194, 26879370, 21415077; Phenotypes: Geleophysic dysplasia 1, MIM# 231050, Dermatosparaxic Ehlers Danlos syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7914 UNC45A Zornitza Stark Phenotypes for gene: UNC45A were changed from Cholestasis; Diarrhoea; Bone fragility; Impaired hearing to Osteootohepatoenteric syndrome, MIM# 619377; Cholestasis; Diarrhoea; Bone fragility; Impaired hearing
Mendeliome v0.7913 UNC45A Zornitza Stark edited their review of gene: UNC45A: Changed phenotypes: Osteootohepatoenteric syndrome, MIM# 619377, Cholestasis, Diarrhoea, Bone fragility, Impaired hearing
Mendeliome v0.7913 EIF5A Zornitza Stark Phenotypes for gene: EIF5A were changed from Intellectual disability; microcephaly; dysmorphism to Faundes-Banka syndrome, MIM# 619376; Intellectual disability; microcephaly; dysmorphism
Mendeliome v0.7912 EIF5A Zornitza Stark edited their review of gene: EIF5A: Changed phenotypes: Faundes-Banka syndrome, MIM# 619376, Intellectual disability, microcephaly, dysmorphism
Mendeliome v0.7912 HS3ST6 Zornitza Stark Marked gene: HS3ST6 as ready
Mendeliome v0.7912 HS3ST6 Zornitza Stark Gene: hs3st6 has been classified as Red List (Low Evidence).
Mendeliome v0.7912 HS3ST6 Zornitza Stark gene: HS3ST6 was added
gene: HS3ST6 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HS3ST6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HS3ST6 were set to 33508266
Phenotypes for gene: HS3ST6 were set to Hereditary angioedema-8 (HAE8), MIM#619367
Review for gene: HS3ST6 was set to RED
Added comment: Three affected individuals from a single family reported, missense variant, no functional data.
Sources: Expert list
Mendeliome v0.7911 MYOF Zornitza Stark Gene: myof has been classified as Red List (Low Evidence).
Mendeliome v0.7911 MYOF Zornitza Stark gene: MYOF was added
gene: MYOF was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MYOF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYOF were set to 32542751
Phenotypes for gene: MYOF were set to Hereditary angioedema-7 (HAE7), MIM#619366
Review for gene: MYOF was set to RED
Added comment: Three individuals from one family reported, onset of recurrent episodic swelling of the face, lips, and oral mucosa was in the second decade. Variant was also present in another unaffected family member. Some functional data.
Sources: Expert list
Mendeliome v0.7910 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7910 KNG1 Zornitza Stark Phenotypes for gene: KNG1 were changed from to Hereditary angioedema-6 (HAE6), MIM#619363
Mendeliome v0.7909 KNG1 Zornitza Stark Publications for gene: KNG1 were set to
Mendeliome v0.7908 KNG1 Zornitza Stark Mode of inheritance for gene: KNG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7907 KNG1 Zornitza Stark Classified gene: KNG1 as Amber List (moderate evidence)
Mendeliome v0.7907 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7906 KNG1 Zornitza Stark reviewed gene: KNG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31087670, 33114181; Phenotypes: Hereditary angioedema-6 (HAE6), MIM#619363; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7906 ANGPT1 Zornitza Stark Marked gene: ANGPT1 as ready
Mendeliome v0.7906 ANGPT1 Zornitza Stark Gene: angpt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7906 ANGPT1 Zornitza Stark Phenotypes for gene: ANGPT1 were changed from Hereditary angioedema to Hereditary angioedema-5 (HAE5), MIM#619361
Mendeliome v0.7905 ANGPT1 Zornitza Stark reviewed gene: ANGPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary angioedema-5 (HAE5), MIM#619361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7905 PLG Zornitza Stark changed review comment from: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. At least 3 unrelated families reported.; to: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. Over 20 unrelated families reported.
Mendeliome v0.7905 PLG Zornitza Stark edited their review of gene: PLG: Changed publications: 28795768, 29548426, 29987869, 9242524, 10233898, 21174000, 21174000
Mendeliome v0.7905 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Mendeliome v0.7905 PLG Zornitza Stark Phenotypes for gene: PLG were changed from to Hereditary angioedema-4 (HAE4), MIM#619360; Plasminogen deficiency, type I, MIM# 217090
Mendeliome v0.7904 PLG Zornitza Stark Publications for gene: PLG were set to
Mendeliome v0.7903 PLG Zornitza Stark Mode of inheritance for gene: PLG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7902 PLG Zornitza Stark reviewed gene: PLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 28795768, 29548426, 29987869, 9242524, 10233898; Phenotypes: Hereditary angioedema-4 (HAE4), MIM#619360, Plasminogen deficiency, type I, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7902 POU4F1 Zornitza Stark Phenotypes for gene: POU4F1 were changed from Ataxia; intention tremor; hypotonia to Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352
Mendeliome v0.7901 POU4F1 Zornitza Stark reviewed gene: POU4F1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) , MIM#619352; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7901 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from Congenital heart defects and ectodermal dysplasia, 617364 to Congenital heart defects and ectodermal dysplasia, 617364; Congenital heart disease, autosomal recessive
Mendeliome v0.7900 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907; 32817298
Mendeliome v0.7899 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7898 PIGF Zornitza Stark Phenotypes for gene: PIGF were changed from Glycosylphosphatidylinositol\ deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures to Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM# 619356
Mendeliome v0.7897 PIGF Zornitza Stark reviewed gene: PIGF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM# 619356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7897 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: Additional publications supporting association with bi-allelic disease:

PMID: 33919081: Three sisters with pulmonary stenosis, truncus arteriosis, and atrial septal defect were homozygous for c.265-1G>T. Their asymptomatic father was also homozygous, however he had two affected sisters (not genotyped), raising the possibility that PRKD1 may undergo autosomal recessive inheritance mode with gender limitation. PMID: 25713110: Two sisters with truncus arteriosis were homozygous for R618X.; Changed publications: 27479907, 32817298, 25713110, 33919081; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7897 ATXN2L Seb Lunke Marked gene: ATXN2L as ready
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7897 ATXN2L Seb Lunke Classified gene: ATXN2L as Amber List (moderate evidence)
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7896 ATXN2L Seb Lunke gene: ATXN2L was added
gene: ATXN2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATXN2L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN2L were set to 33283965; 33057194
Phenotypes for gene: ATXN2L were set to macrocephaly; intellectual disability
Review for gene: ATXN2L was set to AMBER
Added comment: Sources: Literature
Mendeliome v0.7895 LTBP1 Seb Lunke Marked gene: LTBP1 as ready
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7895 LTBP1 Seb Lunke Classified gene: LTBP1 as Green List (high evidence)
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7894 SLC30A5 Seb Lunke Classified gene: SLC30A5 as Amber List (moderate evidence)
Mendeliome v0.7894 SLC30A5 Seb Lunke Gene: slc30a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 SLC30A5 Seb Lunke Gene: slc30a5 has been removed from the panel.
Mendeliome v0.7893 CADM3 Seb Lunke Added comment: Comment when marking as ready: Three families, but evidence not that great and missing segregation, so stays amber.
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 CADM3 Seb Lunke Classified gene: CADM3 as Amber List (moderate evidence)
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Classified gene: PGM2L1 as Green List (high evidence)
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7891 BCAS3 Sue White Gene: bcas3 has been classified as Green List (High Evidence).
Mendeliome v0.7891 RELN Ee Ming Wong reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25648840; Phenotypes: Myoclonus dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.7891 TUBA1A Kristin Rigbye edited their review of gene: TUBA1A: Changed phenotypes: Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7891 TUBA1A Kristin Rigbye reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30677308; Phenotypes: Congenital fibrosis of the extraocular muscles; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7891 PGM2L1 Chern Lim reviewed gene: PGM2L1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33979636; Phenotypes: Neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7891 PGM2L1 Chern Lim Deleted their review
Mendeliome v0.7891 LTBP1 Chern Lim gene: LTBP1 was added
gene: LTBP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP1 were set to 33991472
Phenotypes for gene: LTBP1 were set to cutis laxa syndrome
Review for gene: LTBP1 was set to GREEN
gene: LTBP1 was marked as current diagnostic
Added comment: PMID:33991472
- Premature truncating variants in multiple affected individuals from 4 unrelated consanguineous families.
- Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly).
- Functional studies done on patient fibroblasts and zebrafish models.
Sources: Literature
Mendeliome v0.7891 SLC30A5 Melanie Marty gene: SLC30A5 was added
gene: SLC30A5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A5 were set to 33547425; 12095919
Phenotypes for gene: SLC30A5 were set to Perinatal lethal cardiomyopathy
Review for gene: SLC30A5 was set to AMBER
Added comment: Four affected children from two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. 2 different homozygous PTCs variants found. Knockout of SLC30A5 in mouse models showed reduced body growth and reduced bone density. About 60% of the mice died due to bradyarrhythmia.
Sources: Literature
Mendeliome v0.7891 SRCAP Paul De Fazio reviewed gene: SRCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33909990; Phenotypes: Floating-Harbor syndrome MIM#136140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.7891 COL9A3 Kristin Rigbye reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, AD, MIM# 600969, Stickler syndrome, AR, Deafness, AD, Peripheral vitreoretinal degeneration and retinal detachment, AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7891 BCAS3 Paul De Fazio reviewed gene: BCAS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34022130; Phenotypes: Syndromic neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7891 CADM3 Teresa Zhao gene: CADM3 was added
gene: CADM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CADM3 were set to PMID: 33889941
Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease
Review for gene: CADM3 was set to AMBER
Added comment: Three families reported with the same missense variant in CADM3 p.Tyr172Cys (one family de novo), with mice work to show reduced expression of the mutant protein in axons and abnormal axonal organization.
Sources: Literature
Mendeliome v0.7891 ANGPTL8 Dean Phelan gene: ANGPTL8 was added
gene: ANGPTL8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANGPTL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPTL8 were set to PMID: 33909604
Phenotypes for gene: ANGPTL8 were set to Low serum triglycerides; Coronary artery disease
Review for gene: ANGPTL8 was set to RED
Added comment: PMID: 33909604 - Population studies showed PTV are associated with both lipid levels and coronary artery disease.
Sources: Literature
Mendeliome v0.7891 PGM2L1 Chern Lim gene: PGM2L1 was added
gene: PGM2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM2L1 were set to 33979636
Phenotypes for gene: PGM2L1 were set to severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris
Review for gene: PGM2L1 was set to GREEN
gene: PGM2L1 was marked as current diagnostic
Added comment: PMID: 33979636:
- Hom/chet PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Sources: Literature
Mendeliome v0.7891 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Mendeliome v0.7891 KCNB1 Zornitza Stark Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
Mendeliome v0.7890 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to
Mendeliome v0.7889 KCNB1 Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7888 KCNB1 Zornitza Stark reviewed gene: KCNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600826, 31513310; Phenotypes: Epileptic encephalopathy, early infantile, 26, MIM# 616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7888 SYT1 Zornitza Stark Marked gene: SYT1 as ready
Mendeliome v0.7888 SYT1 Zornitza Stark Gene: syt1 has been classified as Green List (High Evidence).
Mendeliome v0.7888 SYT1 Zornitza Stark Phenotypes for gene: SYT1 were changed from to Baker-Gordon syndrome, MIM# 618218; MONDO:0033864
Mendeliome v0.7887 SYT1 Zornitza Stark Publications for gene: SYT1 were set to
Mendeliome v0.7886 SYT1 Zornitza Stark Mode of inheritance for gene: SYT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7885 SYT1 Zornitza Stark reviewed gene: SYT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30107533; Phenotypes: Baker-Gordon syndrome, MIM# 618218, MONDO:0033864; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7885 UBTF Zornitza Stark Marked gene: UBTF as ready
Mendeliome v0.7885 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Mendeliome v0.7885 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; MONDO:0044701
Mendeliome v0.7884 UBTF Zornitza Stark Publications for gene: UBTF were set to
Mendeliome v0.7883 UBTF Zornitza Stark Mode of inheritance for gene: UBTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7882 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777933, 29300972; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672, MONDO:0044701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7882 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Mendeliome v0.7882 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from Mowat-Wilson syndrome (MIM#235730) to Mowat-Wilson syndrome, MIM# 235730; MONDO:0009341
Mendeliome v0.7881 ZEB2 Zornitza Stark Tag SV/CNV tag was added to gene: ZEB2.
Mendeliome v0.7881 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Mendeliome v0.7881 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278
Mendeliome v0.7880 SLC9A6 Zornitza Stark Publications for gene: SLC9A6 were set to
Mendeliome v0.7879 SLC9A6 Zornitza Stark Mode of inheritance for gene: SLC9A6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7878 SLC9A6 Zornitza Stark reviewed gene: SLC9A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 18342287, 19377476, 25044251, 33278113, 32569089, 31879735; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243, MONDO:0010278; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7878 RPL3L Zornitza Stark Phenotypes for gene: RPL3L were changed from Neonatal dilated cardiomyopathy to Cardiomyopathy, dilated, 2D, MIM# 619371; Neonatal dilated cardiomyopathy
Mendeliome v0.7877 RPL3L Zornitza Stark reviewed gene: RPL3L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 2D, MIM# 619371, Neonatal dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7877 SHANK3 Zornitza Stark Publications for gene: SHANK3 were set to 30842224
Mendeliome v0.7876 SHANK3 Zornitza Stark Tag SV/CNV tag was added to gene: SHANK3.
Mendeliome v0.7876 SHANK3 Zornitza Stark reviewed gene: SHANK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16284256, 17173049, 20186804, 22892527; Phenotypes: Phelan-McDermid syndrome, MIM# 606232; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7876 SHANK3 Zornitza Stark Phenotypes for gene: SHANK3 were changed from Phelan-McDermid syndrome 606232; Rett syndrome; Rett-like phenotypes to Phelan-McDermid syndrome 606232; MONDO:0011652
Mendeliome v0.7875 SATB2 Zornitza Stark Marked gene: SATB2 as ready
Mendeliome v0.7875 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Mendeliome v0.7875 SATB2 Zornitza Stark Phenotypes for gene: SATB2 were changed from to Glass syndrome, MIM# 612313; MONDO:0100147
Mendeliome v0.7874 SATB2 Zornitza Stark Publications for gene: SATB2 were set to
Mendeliome v0.7873 SATB2 Zornitza Stark Mode of inheritance for gene: SATB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7872 SATB2 Zornitza Stark reviewed gene: SATB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29023086, 28151491, 32446642; Phenotypes: Glass syndrome, MIM# 612313, MONDO:0100147; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7872 MEF2C Zornitza Stark Tag SV/CNV tag was added to gene: MEF2C.
Tag 5'UTR tag was added to gene: MEF2C.
Mendeliome v0.7872 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443 to Chromosome 5q14.3 deletion syndrome, 613443; Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443; MONDO:0013266
Mendeliome v0.7871 MEF2C Zornitza Stark Publications for gene: MEF2C were set to
Mendeliome v0.7870 MEF2C Zornitza Stark reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: 19876902, 19471318, 19592390, 19592390, 20513142, 34055696, 34022131; Phenotypes: Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, MIM# 613443, MONDO:0013266 Edit; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7870 MBD5 Zornitza Stark Tag SV/CNV tag was added to gene: MBD5.
Mendeliome v0.7870 MBD5 Zornitza Stark Gene: mbd5 has been classified as Green List (High Evidence).
Mendeliome v0.7870 MBD5 Zornitza Stark Phenotypes for gene: MBD5 were changed from to Mental retardation, autosomal dominant 1, MIM# 156200; MONDO:0007974
Mendeliome v0.7869 MBD5 Zornitza Stark Publications for gene: MBD5 were set to
Mendeliome v0.7868 MBD5 Zornitza Stark Mode of inheritance for gene: MBD5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7867 MBD5 Zornitza Stark reviewed gene: MBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 18812405, 21981781, 23708187, 22726846, 33912662; Phenotypes: Mental retardation, autosomal dominant 1, MIM# 156200, MONDO:0007974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7867 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM#309530 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v0.7866 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 31415821; 20473311; 30842726
Mendeliome v0.7865 IQSEC2 Zornitza Stark reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33368194, 20473311, 23674175; Phenotypes: Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656, Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347; 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 v0.7865 EEF1A2 Zornitza Stark Phenotypes for gene: EEF1A2 were changed from Epileptic encephalopathy, early infantile, 33, MIM# 616409; Mental retardation, autosomal dominant 38, MIM# 616393 to Mental retardation, autosomal dominant 38, MIM# 616393; MONDO:0014617; Developmental and epileptic encephalopathy 33, MIM# 616409; MONDO:0014625
Mendeliome v0.7864 EEF1A2 Zornitza Stark Publications for gene: EEF1A2 were set to 32160274
Mendeliome v0.7863 EEF1A2 Zornitza Stark reviewed gene: EEF1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24697219, 32196822, 32160274, 32062104, 31893083; Phenotypes: Mental retardation, autosomal dominant 38, MIM# 616393, MONDO:0014617, Developmental and epileptic encephalopathy 33, MIM# 616409, MONDO:0014625; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7863 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Mendeliome v0.7863 MASP1 Zornitza Stark Phenotypes for gene: MASP1 were changed from to 3MC syndrome 1, MIM# 257920; MONDO:0009770
Mendeliome v0.7862 MASP1 Zornitza Stark Publications for gene: MASP1 were set to
Mendeliome v0.7861 MASP1 Zornitza Stark Mode of inheritance for gene: MASP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7860 MASP1 Zornitza Stark reviewed gene: MASP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26789649, 21258343, 21035106; Phenotypes: 3MC syndrome 1, MIM# 257920, MONDO:0009770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7860 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Mendeliome v0.7860 BRPF1 Zornitza Stark Phenotypes for gene: BRPF1 were changed from to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333; MONDO:0015022
Mendeliome v0.7859 BRPF1 Zornitza Stark Publications for gene: BRPF1 were set to
Mendeliome v0.7858 BRPF1 Zornitza Stark Mode of inheritance for gene: BRPF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7857 BRPF1 Zornitza Stark reviewed gene: BRPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27939640, 27939639; Phenotypes: Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333, MONDO:0015022; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7857 TRAF7 Zornitza Stark Marked gene: TRAF7 as ready
Mendeliome v0.7857 TRAF7 Zornitza Stark Gene: traf7 has been classified as Green List (High Evidence).
Mendeliome v0.7857 TRAF7 Zornitza Stark Phenotypes for gene: TRAF7 were changed from to Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164
Mendeliome v0.7856 TRAF7 Zornitza Stark Publications for gene: TRAF7 were set to
Mendeliome v0.7855 TRAF7 Zornitza Stark Mode of inheritance for gene: TRAF7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7854 TRAF7 Zornitza Stark reviewed gene: TRAF7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32376980; Phenotypes: Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7854 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Mendeliome v0.7854 UBE3B Zornitza Stark Phenotypes for gene: UBE3B were changed from to Kaufman oculocerebrofacial syndrome, MIM# 244450; MONDO:0009485
Mendeliome v0.7853 UBE3B Zornitza Stark Publications for gene: UBE3B were set to
Mendeliome v0.7852 UBE3B Zornitza Stark Mode of inheritance for gene: UBE3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7851 UBE3B Zornitza Stark reviewed gene: UBE3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23200864, 23200864, 34012380, 32949109; Phenotypes: Kaufman oculocerebrofacial syndrome, MIM# 244450, MONDO:0009485; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7851 HSPG2 Zornitza Stark Publications for gene: HSPG2 were set to 16927315
Mendeliome v0.7850 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11101850, 16927315, 11279527; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, MONDO:0009717, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410, MONDO:0009140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Classified gene: HLA-DRB1 as Red List (low evidence)
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRB1 Zornitza Stark reviewed gene: HLA-DRB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRA Zornitza Stark Classified gene: HLA-DRA as Red List (low evidence)
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-DRA Zornitza Stark reviewed gene: HLA-DRA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-C Zornitza Stark Classified gene: HLA-C as Red List (low evidence)
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-C Zornitza Stark reviewed gene: HLA-C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-B Zornitza Stark Classified gene: HLA-B as Red List (low evidence)
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-B Zornitza Stark reviewed gene: HLA-B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-A Zornitza Stark Classified gene: HLA-A as Red List (low evidence)
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7845 HLA-A Zornitza Stark reviewed gene: HLA-A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7845 TAF6 Zornitza Stark Marked gene: TAF6 as ready
Mendeliome v0.7845 TAF6 Zornitza Stark Gene: taf6 has been classified as Green List (High Evidence).
Mendeliome v0.7845 TAF6 Zornitza Stark Phenotypes for gene: TAF6 were changed from to Alazami-Yuan syndrome, MIM# 617126
Mendeliome v0.7844 TAF6 Zornitza Stark Publications for gene: TAF6 were set to
Mendeliome v0.7843 TAF6 Zornitza Stark Mode of inheritance for gene: TAF6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7842 TAF6 Zornitza Stark reviewed gene: TAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25558065, 25574841, 32030742; Phenotypes: Alazami-Yuan syndrome, MIM# 617126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7842 ANGPT2 Zornitza Stark Phenotypes for gene: ANGPT2 were changed from Primary lymphoedema to Lymphatic malformation-10, MIM#619369; Primary lymphoedema
Mendeliome v0.7841 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Changed phenotypes: Lymphatic malformation-10, MIM#619369, Primary lymphoedema
Mendeliome v0.7841 SLC24A5 Zornitza Stark Gene: slc24a5 has been classified as Green List (High Evidence).
Mendeliome v0.7841 SLC24A5 Zornitza Stark Phenotypes for gene: SLC24A5 were changed from to Albinism, oculocutaneous, type VI, MIM# 113750
Mendeliome v0.7840 SLC24A5 Zornitza Stark Publications for gene: SLC24A5 were set to
Mendeliome v0.7839 SLC24A5 Zornitza Stark Mode of inheritance for gene: SLC24A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7838 SLC24A5 Zornitza Stark reviewed gene: SLC24A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23364476, 23985994, 26491832; Phenotypes: Albinism, oculocutaneous, type VI, MIM# 113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7838 SLC45A2 Zornitza Stark Gene: slc45a2 has been classified as Green List (High Evidence).
Mendeliome v0.7838 SLC45A2 Zornitza Stark Phenotypes for gene: SLC45A2 were changed from to Albinism, oculocutaneous, type IV, MIM# 606574; MONDO:0011683
Mendeliome v0.7837 SLC45A2 Zornitza Stark Publications for gene: SLC45A2 were set to
Mendeliome v0.7836 SLC45A2 Zornitza Stark Mode of inheritance for gene: SLC45A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7835 SLC45A2 Zornitza Stark reviewed gene: SLC45A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11574907, 14722913, 14961451; Phenotypes: Albinism, oculocutaneous, type IV, MIM# 606574, MONDO:0011683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7835 TYR Zornitza Stark Marked gene: TYR as ready
Mendeliome v0.7835 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Mendeliome v0.7835 TYR Zornitza Stark Phenotypes for gene: TYR were changed from to Albinism, oculocutaneous, type IA, MIM# 203100; MONDO:0008745; Albinism, oculocutaneous, type IB, MIM# 606952
Mendeliome v0.7834 TYR Zornitza Stark Mode of inheritance for gene: TYR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7833 TYR Zornitza Stark reviewed gene: TYR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Albinism, oculocutaneous, type IA, MIM# 203100, MONDO:0008745, Albinism, oculocutaneous, type IB, MIM# 606952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7833 TYRP1 Zornitza Stark Marked gene: TYRP1 as ready
Mendeliome v0.7833 TYRP1 Zornitza Stark Gene: tyrp1 has been classified as Green List (High Evidence).
Mendeliome v0.7833 TYRP1 Zornitza Stark Phenotypes for gene: TYRP1 were changed from to Albinism, oculocutaneous, type III, MIM# 203290; MONDO:0008747
Mendeliome v0.7832 TYRP1 Zornitza Stark Publications for gene: TYRP1 were set to
Mendeliome v0.7831 TYRP1 Zornitza Stark Mode of inheritance for gene: TYRP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7830 TYRP1 Zornitza Stark reviewed gene: TYRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9345097; Phenotypes: Albinism, oculocutaneous, type III, MIM# 203290, MONDO:0008747; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7830 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7830 MC1R Zornitza Stark Phenotypes for gene: MC1R were changed from to {Albinism, oculocutaneous, type II, modifier of}, MIM# 203200
Mendeliome v0.7829 MC1R Zornitza Stark Publications for gene: MC1R were set to
Mendeliome v0.7828 MC1R Zornitza Stark Mode of inheritance for gene: MC1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7827 MC1R Zornitza Stark Classified gene: MC1R as Amber List (moderate evidence)
Mendeliome v0.7827 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7826 MC1R Zornitza Stark reviewed gene: MC1R: Rating: AMBER; Mode of pathogenicity: None; Publications: 12876664; Phenotypes: {Albinism, oculocutaneous, type II, modifier of}, MIM# 203200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7826 LRMDA Zornitza Stark Gene: lrmda has been classified as Green List (High Evidence).
Mendeliome v0.7826 LRMDA Zornitza Stark Phenotypes for gene: LRMDA were changed from to Albinism, oculocutaneous, type VII, MIM# 615179; MONDO:0014070
Mendeliome v0.7825 LRMDA Zornitza Stark Publications for gene: LRMDA were set to
Mendeliome v0.7824 LRMDA Zornitza Stark Mode of inheritance for gene: LRMDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7823 LRMDA Zornitza Stark reviewed gene: LRMDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23395477; Phenotypes: Albinism, oculocutaneous, type VII, MIM# 615179, MONDO:0014070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7823 SERPINF2 Zornitza Stark Gene: serpinf2 has been classified as Green List (High Evidence).
Mendeliome v0.7823 SERPINF2 Zornitza Stark Phenotypes for gene: SERPINF2 were changed from to Alpha-2-plasmin inhibitor deficiency, MIM# 262850
Mendeliome v0.7822 SERPINF2 Zornitza Stark Publications for gene: SERPINF2 were set to
Mendeliome v0.7821 SERPINF2 Zornitza Stark Mode of inheritance for gene: SERPINF2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7820 SERPINF2 Zornitza Stark reviewed gene: SERPINF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 2572590, 10583218, 31441040, 31282989, 29656168; Phenotypes: Alpha-2-plasmin inhibitor deficiency, MIM# 262850; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7820 SERPINE1 Zornitza Stark Gene: serpine1 has been classified as Green List (High Evidence).
Mendeliome v0.7820 SERPINE1 Zornitza Stark Phenotypes for gene: SERPINE1 were changed from to Plasminogen activator inhibitor-1 deficiency, MIM# 613329
Mendeliome v0.7819 SERPINE1 Zornitza Stark Publications for gene: SERPINE1 were set to
Mendeliome v0.7818 SERPINE1 Zornitza Stark Mode of inheritance for gene: SERPINE1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.7817 SERPINE1 Zornitza Stark reviewed gene: SERPINE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9207454, 15650551; Phenotypes: Plasminogen activator inhibitor-1 deficiency, MIM# 613329; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.7817 TBXA2R Zornitza Stark Marked gene: TBXA2R as ready
Mendeliome v0.7817 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7817 TBXA2R Zornitza Stark Phenotypes for gene: TBXA2R were changed from to {Bleeding disorder, platelet-type, 13, susceptibility to}, MIM# 614009
Mendeliome v0.7816 TBXA2R Zornitza Stark Publications for gene: TBXA2R were set to
Mendeliome v0.7815 TBXA2R Zornitza Stark Mode of inheritance for gene: TBXA2R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7814 TBXA2R Zornitza Stark Classified gene: TBXA2R as Amber List (moderate evidence)
Mendeliome v0.7814 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7813 TBXA2R Zornitza Stark reviewed gene: TBXA2R: Rating: AMBER; Mode of pathogenicity: None; Publications: 7929844, 19828703, 22517902; Phenotypes: {Bleeding disorder, platelet-type, 13, susceptibility to}, MIM# 614009; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7813 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Green List (High Evidence).
Mendeliome v0.7813 P2RY12 Zornitza Stark Phenotypes for gene: P2RY12 were changed from to Bleeding disorder, platelet-type, 8, MIM# 609821; MONDO:0012354
Mendeliome v0.7812 P2RY12 Zornitza Stark Publications for gene: P2RY12 were set to
Mendeliome v0.7811 P2RY12 Zornitza Stark Mode of inheritance for gene: P2RY12 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7810 P2RY12 Zornitza Stark reviewed gene: P2RY12: Rating: GREEN; Mode of pathogenicity: None; Publications: 11196645, 12578987, 29117459, 19237732; Phenotypes: Bleeding disorder, platelet-type, 8, MIM# 609821, MONDO:0012354; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7810 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
Mendeliome v0.7810 MCFD2 Zornitza Stark Phenotypes for gene: MCFD2 were changed from to Factor V and factor VIII, combined deficiency of, MIM# 613625; MONDO:0013331
Mendeliome v0.7809 MCFD2 Zornitza Stark Publications for gene: MCFD2 were set to
Mendeliome v0.7808 MCFD2 Zornitza Stark Mode of inheritance for gene: MCFD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7807 MCFD2 Zornitza Stark reviewed gene: MCFD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12717434, 16304051, 18391077; Phenotypes: Factor V and factor VIII, combined deficiency of, MIM# 613625, MONDO:0013331; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7807 LMAN1 Zornitza Stark Gene: lman1 has been classified as Green List (High Evidence).
Mendeliome v0.7807 LMAN1 Zornitza Stark Phenotypes for gene: LMAN1 were changed from to Combined factor V and VIII deficiency, MIM# 227300; MONDO:0009206
Mendeliome v0.7806 LMAN1 Zornitza Stark Publications for gene: LMAN1 were set to
Mendeliome v0.7805 LMAN1 Zornitza Stark Mode of inheritance for gene: LMAN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7804 LMAN1 Zornitza Stark reviewed gene: LMAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9546392, 16304051; Phenotypes: Combined factor V and VIII deficiency, MIM# 227300, MONDO:0009206; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7804 ITGA2B Zornitza Stark Marked gene: ITGA2B as ready
Mendeliome v0.7804 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
Mendeliome v0.7804 ITGA2B Zornitza Stark Phenotypes for gene: ITGA2B were changed from to Bleeding disorder, platelet-type, 16, MIM# 187800; MONDO:000855; Glanzmann thrombasthaenia 1, MIM# 273800
Mendeliome v0.7803 ITGA2B Zornitza Stark Publications for gene: ITGA2B were set to
Mendeliome v0.7802 ITGA2B Zornitza Stark Mode of inheritance for gene: ITGA2B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7801 ITGA2B Zornitza Stark reviewed gene: ITGA2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 1638023, 21454453, 8282784, 16463284; Phenotypes: Bleeding disorder, platelet-type, 16, MIM# 187800, MONDO:000855, Glanzmann thrombasthaenia 1, MIM# 273800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7801 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7801 LMOD1 Zornitza Stark Phenotypes for gene: LMOD1 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362
Mendeliome v0.7800 LMOD1 Zornitza Stark Publications for gene: LMOD1 were set to
Mendeliome v0.7799 LMOD1 Zornitza Stark Mode of inheritance for gene: LMOD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7798 LMOD1 Zornitza Stark Classified gene: LMOD1 as Amber List (moderate evidence)
Mendeliome v0.7798 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7797 LMOD1 Zornitza Stark reviewed gene: LMOD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28292896; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7797 POU4F1 Bryony Thompson Classified gene: POU4F1 as Green List (high evidence)
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7796 POU4F1 Bryony Thompson gene: POU4F1 was added
gene: POU4F1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU4F1 were set to 33783914; 8876243
Phenotypes for gene: POU4F1 were set to Ataxia; intention tremor; hypotonia
Review for gene: POU4F1 was set to GREEN
Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model.
Sources: Literature
Mendeliome v0.7795 HPS6 Zornitza Stark Gene: hps6 has been classified as Green List (High Evidence).
Mendeliome v0.7795 HPS6 Zornitza Stark Phenotypes for gene: HPS6 were changed from to Hermansky-Pudlak syndrome 6, MIM# 614075; MONDO:0013558
Mendeliome v0.7794 HPS6 Zornitza Stark Publications for gene: HPS6 were set to
Mendeliome v0.7793 HPS6 Zornitza Stark Mode of inheritance for gene: HPS6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7792 HPS6 Zornitza Stark reviewed gene: HPS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 12548288, 17041891, 19843503; Phenotypes: Hermansky-Pudlak syndrome 6, MIM# 614075, MONDO:0013558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7792 HPS4 Zornitza Stark Gene: hps4 has been classified as Green List (High Evidence).
Mendeliome v0.7792 HPS4 Zornitza Stark Publications for gene: HPS4 were set to
Mendeliome v0.7791 HPS4 Zornitza Stark Phenotypes for gene: HPS4 were changed from to Hermansky-Pudlak syndrome 4, MIM# 614073; MONDO:0013556
Mendeliome v0.7790 HPS4 Zornitza Stark Mode of inheritance for gene: HPS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7789 HPS4 Zornitza Stark reviewed gene: HPS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11836498, 12664304; Phenotypes: Hermansky-Pudlak syndrome 4, MIM# 614073, MONDO:0013556; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7789 HPS3 Zornitza Stark Gene: hps3 has been classified as Green List (High Evidence).
Mendeliome v0.7789 HPS3 Zornitza Stark Phenotypes for gene: HPS3 were changed from to Hermansky-Pudlak syndrome 3, MIM# 614072; MONDO:0013555
Mendeliome v0.7788 HPS3 Zornitza Stark Publications for gene: HPS3 were set to
Mendeliome v0.7787 HPS3 Zornitza Stark Mode of inheritance for gene: HPS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7786 HPS3 Zornitza Stark reviewed gene: HPS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11455388, 31880485, 31621111, 30990103; Phenotypes: Hermansky-Pudlak syndrome 3, MIM# 614072, MONDO:0013555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7786 HPS1 Zornitza Stark Gene: hps1 has been classified as Green List (High Evidence).
Mendeliome v0.7786 HPS1 Zornitza Stark Phenotypes for gene: HPS1 were changed from to Hermansky-Pudlak syndrome 1, MIM# 203300; MONDO:0008748
Mendeliome v0.7785 HPS1 Zornitza Stark Publications for gene: HPS1 were set to
Mendeliome v0.7784 HPS1 Zornitza Stark Mode of inheritance for gene: HPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7783 HPS1 Zornitza Stark reviewed gene: HPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9497254; Phenotypes: Hermansky-Pudlak syndrome 1, MIM# 203300, MONDO:0008748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7783 GP9 Zornitza Stark Gene: gp9 has been classified as Green List (High Evidence).
Mendeliome v0.7783 GP9 Zornitza Stark Phenotypes for gene: GP9 were changed from to Bernard-Soulier syndrome, type C, MIM# 231200
Mendeliome v0.7782 GP9 Zornitza Stark Publications for gene: GP9 were set to
Mendeliome v0.7781 GP9 Zornitza Stark Mode of inheritance for gene: GP9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7780 GP9 Zornitza Stark reviewed gene: GP9: Rating: GREEN; Mode of pathogenicity: None; Publications: 8049428, 33553065, 32030720, 31484196; Phenotypes: Bernard-Soulier syndrome, type C, MIM# 231200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7780 GP6 Zornitza Stark Gene: gp6 has been classified as Green List (High Evidence).
Mendeliome v0.7780 GP6 Zornitza Stark Phenotypes for gene: GP6 were changed from to Bleeding disorder, platelet-type, 11, MIM# 614201; MONDO:0013623
Mendeliome v0.7779 GP6 Zornitza Stark Publications for gene: GP6 were set to
Mendeliome v0.7778 GP6 Zornitza Stark Mode of inheritance for gene: GP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7777 GP6 Zornitza Stark reviewed gene: GP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 19549989, 19552682, 23815599; Phenotypes: Bleeding disorder, platelet-type, 11, MIM# 614201, MONDO:0013623; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7777 GP1BB Zornitza Stark Gene: gp1bb has been classified as Green List (High Evidence).
Mendeliome v0.7777 GP1BB Zornitza Stark Phenotypes for gene: GP1BB were changed from to Bernard-Soulier syndrome, type B, MIM# 231200; Macrothrombocytopaenia
Mendeliome v0.7776 GP1BB Zornitza Stark Publications for gene: GP1BB were set to
Mendeliome v0.7775 GP1BB Zornitza Stark Mode of inheritance for gene: GP1BB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7774 GP1BB Zornitza Stark reviewed gene: GP1BB: Rating: GREEN; Mode of pathogenicity: None; Publications: 8703016, 9116284, 10887115, 33813986, 33657022, 33216977, 31997307, 1730088, 11222377; Phenotypes: Bernard-Soulier syndrome, type B, MIM# 231200, Macrothrombocytopaenia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7774 CREB3L3 Zornitza Stark Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7774 CREB3L3 Zornitza Stark Phenotypes for gene: CREB3L3 were changed from Hyperlipidaemia; hypertriglyceridemia to Hypertriglyceridaemia-2, MIM#619324
Mendeliome v0.7773 CREB3L3 Zornitza Stark reviewed gene: CREB3L3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertriglyceridaemia-2, MIM#619324; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7773 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness; cataract to Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 PSMC3 Zornitza Stark edited their review of gene: PSMC3: Changed phenotypes: Feafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Mendeliome v0.7772 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Mendeliome v0.7772 SCNN1B Zornitza Stark Phenotypes for gene: SCNN1B were changed from to Liddle syndrome 1, MIM# 177200; Pseudohypoaldosteronism, type I, MIM# 264350; Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400)
Mendeliome v0.7771 SCNN1B Zornitza Stark Mode of inheritance for gene: SCNN1B was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7770 SCNN1B Zornitza Stark reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Liddle syndrome 1, MIM# 177200, Pseudohypoaldosteronism, type I, MIM# 264350, Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7770 FGB Zornitza Stark Gene: fgb has been classified as Green List (High Evidence).
Mendeliome v0.7770 FGB Zornitza Stark Phenotypes for gene: FGB were changed from to Afibrinogenaemia, congenital, MIM# 202400; Hypofibrinogenaemia, congenital, MIM# 202400; Dysfibrinogenaemia, congenital, MIM# 616004
Mendeliome v0.7769 FGB Zornitza Stark Publications for gene: FGB were set to
Mendeliome v0.7768 FGB Zornitza Stark Mode of inheritance for gene: FGB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7767 FGB Zornitza Stark changed review comment from: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both.

Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder. Well established gene-disease association.; to: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both.

Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder.

Well established gene-disease association.
Mendeliome v0.7767 FGB Zornitza Stark reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 12393540, 16195396; Phenotypes: Afibrinogenaemia, congenital, MIM# 202400, Hypofibrinogenaemia, congenital, MIM# 202400, Dysfibrinogenaemia, congenital, MIM# 616004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7767 F9 Zornitza Stark Gene: f9 has been classified as Green List (High Evidence).
Mendeliome v0.7767 F9 Zornitza Stark Phenotypes for gene: F9 were changed from to Haemophilia B, MIM# 306900; Thrombophilia, X-linked, due to factor IX defect, MIM# 300807
Mendeliome v0.7766 F9 Zornitza Stark Publications for gene: F9 were set to
Mendeliome v0.7765 F9 Zornitza Stark Mode of inheritance for gene: F9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7764 F9 Zornitza Stark reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19846852, 34015304, 33656538; Phenotypes: Haemophilia B, MIM# 306900, Thrombophilia, X-linked, due to factor IX defect, MIM# 300807; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7764 F8 Zornitza Stark Gene: f8 has been classified as Green List (High Evidence).
Mendeliome v0.7764 F8 Zornitza Stark Phenotypes for gene: F8 were changed from to Haemophilia A, MIM# 306700; MONDO:0010602
Mendeliome v0.7763 F8 Zornitza Stark Publications for gene: F8 were set to
Mendeliome v0.7762 F8 Zornitza Stark Mode of inheritance for gene: F8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7761 F8 Zornitza Stark reviewed gene: F8: Rating: GREEN; Mode of pathogenicity: None; Publications: 2986011, 3097553; Phenotypes: Haemophilia A, MIM# 306700, MONDO:0010602; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7761 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Mendeliome v0.7761 F7 Zornitza Stark Phenotypes for gene: F7 were changed from to Factor VII deficiency, MIM# 227500; MONDO:0009211
Mendeliome v0.7760 F7 Zornitza Stark Publications for gene: F7 were set to
Mendeliome v0.7759 F7 Zornitza Stark Mode of inheritance for gene: F7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7758 F7 Zornitza Stark reviewed gene: F7: Rating: GREEN; Mode of pathogenicity: None; Publications: 12181036; Phenotypes: Factor VII deficiency, MIM# 227500, MONDO:0009211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7758 F5 Zornitza Stark Gene: f5 has been classified as Green List (High Evidence).
Mendeliome v0.7758 F5 Zornitza Stark Phenotypes for gene: F5 were changed from to Factor V deficiency, MIM# 227400; MONDO:0009210; Thrombophilia due to activated protein C resistance, MIM# 188055; MONDO:0008560; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055
Mendeliome v0.7757 F5 Zornitza Stark Mode of inheritance for gene: F5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7756 F5 Zornitza Stark reviewed gene: F5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency, MIM# 227400, MONDO:0009210, Thrombophilia due to activated protein C resistance, MIM# 188055, MONDO:0008560, {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7756 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Mendeliome v0.7756 F13A1 Zornitza Stark Phenotypes for gene: F13A1 were changed from to Factor XIIIA deficiency, MIM# 613225; MONDO:0013187
Mendeliome v0.7755 F13A1 Zornitza Stark Publications for gene: F13A1 were set to
Mendeliome v0.7754 F13A1 Zornitza Stark Mode of inheritance for gene: F13A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7753 F13A1 Zornitza Stark reviewed gene: F13A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1644910, 7727776, 10027709, 33802692, 32060721; Phenotypes: Factor XIIIA deficiency, MIM# 613225, MONDO:0013187; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7753 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Mendeliome v0.7753 F10 Zornitza Stark Phenotypes for gene: F10 were changed from to Factor X deficiency, MIM# 227600; MONDO:0009212
Mendeliome v0.7752 F10 Zornitza Stark Publications for gene: F10 were set to
Mendeliome v0.7751 F10 Zornitza Stark Mode of inheritance for gene: F10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7750 F10 Zornitza Stark Deleted their comment
Mendeliome v0.7750 F10 Zornitza Stark commented on gene: F10: Factor X deficiency shows variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally haemarthrosis. More than 20 unrelated families reported.
Mendeliome v0.7750 F10 Zornitza Stark reviewed gene: F10: Rating: GREEN; Mode of pathogenicity: None; Publications: 2790181, 2567188, 10746568, 12028042; Phenotypes: Factor X deficiency, MIM# 227600, MONDO:0009212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7750 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7749 MCM7 Arina Puzriakova gene: MCM7 was added
gene: MCM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present.
------
Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment.
Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Mendeliome v0.7749 DTNBP1 Zornitza Stark Marked gene: DTNBP1 as ready
Mendeliome v0.7749 DTNBP1 Zornitza Stark Gene: dtnbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7749 DTNBP1 Zornitza Stark Phenotypes for gene: DTNBP1 were changed from to Hermansky-Pudlak syndrome 7, MIM# 614076; MONDO:0013559
Mendeliome v0.7748 DTNBP1 Zornitza Stark Publications for gene: DTNBP1 were set to
Mendeliome v0.7747 DTNBP1 Zornitza Stark Mode of inheritance for gene: DTNBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7746 DTNBP1 Zornitza Stark reviewed gene: DTNBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12923531, 23364359, 28259707, 30990103; Phenotypes: Hermansky-Pudlak syndrome 7, MIM# 614076, MONDO:0013559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Gene: bloc1s3 has been classified as Green List (High Evidence).
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Phenotypes for gene: BLOC1S3 were changed from to Hermansky-Pudlak syndrome 8, MIM# 614077; MONDO:0013560
Mendeliome v0.7745 BLOC1S3 Zornitza Stark Publications for gene: BLOC1S3 were set to
Mendeliome v0.7744 BLOC1S3 Zornitza Stark Mode of inheritance for gene: BLOC1S3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7743 BLOC1S3 Zornitza Stark reviewed gene: BLOC1S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16385460, 22709368, 32687635; Phenotypes: Hermansky-Pudlak syndrome 8, MIM# 614077, MONDO:0013560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7743 AP3B1 Zornitza Stark Gene: ap3b1 has been classified as Green List (High Evidence).
Mendeliome v0.7743 AP3B1 Zornitza Stark Phenotypes for gene: AP3B1 were changed from to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997
Mendeliome v0.7742 AP3B1 Zornitza Stark Publications for gene: AP3B1 were set to
Mendeliome v0.7741 AP3B1 Zornitza Stark Mode of inheritance for gene: AP3B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7740 AP3B1 Zornitza Stark reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10024875, 11809908, 14566336; Phenotypes: Hermansky-Pudlak syndrome 2, MIM# 608233, MONDO:0011997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7740 LHCGR Zornitza Stark Gene: lhcgr has been classified as Green List (High Evidence).
Mendeliome v0.7740 LHCGR Zornitza Stark Phenotypes for gene: LHCGR were changed from to Luteinizing hormone resistance, female, (MIM#238320); Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320); Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320); Precocious puberty, male, (MIM#176410)
Mendeliome v0.7739 LHCGR Zornitza Stark Publications for gene: LHCGR were set to
Mendeliome v0.7738 LHCGR Zornitza Stark Mode of inheritance for gene: LHCGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7737 NEB Zornitza Stark Publications for gene: NEB were set to 25205138
Mendeliome v0.7736 NEB Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy 2, autosomal recessive 256030 to Nemaline myopathy 2, autosomal recessive 256030; MONDO:0009725; Arthrogryposis multiplex congenita 6, MIM# 619334
Mendeliome v0.7735 NEB Zornitza Stark reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051637, 22367672, 26578207, 33376055; Phenotypes: Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7735 LHCGR Ain Roesley reviewed gene: LHCGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11041448; Phenotypes: Luteinizing hormone resistance, female, (MIM#238320), Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320), Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320), Precocious puberty, male, (MIM#176410); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7735 GEMIN5 Zornitza Stark Classified gene: GEMIN5 as Green List (high evidence)
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7734 GEMIN5 Zornitza Stark gene: GEMIN5 was added
gene: GEMIN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN5 were set to 33963192
Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333
Review for gene: GEMIN5 was set to GREEN
Added comment: Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. 30 individuals from 22 unrelated families reported.
Sources: Literature
Mendeliome v0.7733 ANO6 Zornitza Stark Gene: ano6 has been classified as Green List (High Evidence).
Mendeliome v0.7733 ANO6 Zornitza Stark Phenotypes for gene: ANO6 were changed from to Scott syndrome, MIM# 262890; MONDO:0009885
Mendeliome v0.7732 ANO6 Zornitza Stark Publications for gene: ANO6 were set to
Mendeliome v0.7731 ANO6 Zornitza Stark Mode of inheritance for gene: ANO6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7730 ANO6 Zornitza Stark reviewed gene: ANO6: Rating: GREEN; Mode of pathogenicity: None; Publications: 21107324, 11895776, 27879994, 27634832; Phenotypes: Scott syndrome, MIM# 262890, MONDO:0009885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7730 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
Mendeliome v0.7730 KLHL3 Zornitza Stark Phenotypes for gene: KLHL3 were changed from to Pseudohypoaldosteronism, type IID, MIM# 614495
Mendeliome v0.7729 KLHL3 Zornitza Stark Publications for gene: KLHL3 were set to
Mendeliome v0.7728 KLHL3 Zornitza Stark Mode of inheritance for gene: KLHL3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7727 KLHL3 Zornitza Stark reviewed gene: KLHL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22266938, 22406640, 24821705, 34022862, 32462939; Phenotypes: Pseudohypoaldosteronism, type IID, MIM# 614495; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7727 KCNJ5 Zornitza Stark Classified gene: KCNJ5 as Green List (high evidence)
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7726 KCNJ5 Zornitza Stark gene: KCNJ5 was added
gene: KCNJ5 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNJ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ5 were set to 21311022; 22203740; 24420545; 24574546
Phenotypes for gene: KCNJ5 were set to Hyperaldosteronism, familial, type III, MIM# 613677
Review for gene: KCNJ5 was set to GREEN
Added comment: Association with hyperaldosteronism: At least 5 unrelated families reported.

Association with Long QT: disputed.
Sources: Expert Review
Mendeliome v0.7725 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
Mendeliome v0.7725 HSD11B2 Zornitza Stark Phenotypes for gene: HSD11B2 were changed from to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025
Mendeliome v0.7724 HSD11B2 Zornitza Stark Publications for gene: HSD11B2 were set to
Mendeliome v0.7723 HSD11B2 Zornitza Stark Mode of inheritance for gene: HSD11B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7722 HSD11B2 Zornitza Stark reviewed gene: HSD11B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7670488, 9683587, 17314322; Phenotypes: Apparent mineralocorticoid excess, MIM# 218030, MONDO:0009025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7722 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Mendeliome v0.7722 CLCN2 Zornitza Stark Phenotypes for gene: CLCN2 were changed from to Leukoencephalopathy with ataxia, MIM# 615651; Hyperaldosteronism, familial, type II, MIM# 605635
Mendeliome v0.7721 CLCN2 Zornitza Stark Publications for gene: CLCN2 were set to
Mendeliome v0.7720 CLCN2 Zornitza Stark Mode of inheritance for gene: CLCN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7719 CLCN2 Zornitza Stark reviewed gene: CLCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29403011, 29403012, 23707145; Phenotypes: Leukoencephalopathy with ataxia, MIM# 615651, Hyperaldosteronism, familial, type II, MIM# 605635; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7719 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Green List (High Evidence).
Mendeliome v0.7719 CACNA1D Zornitza Stark Phenotypes for gene: CACNA1D were changed from to Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; MONDO:0014200; Sinoatrial node dysfunction and deafness, MIM# 614896
Mendeliome v0.7718 CACNA1D Zornitza Stark Publications for gene: CACNA1D were set to
Mendeliome v0.7717 CACNA1D Zornitza Stark Mode of inheritance for gene: CACNA1D was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7716 CACNA1D Zornitza Stark reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913001, 32336187, 30698561, 21131953, 15357422, 22678062; Phenotypes: Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474, MONDO:0014200, Sinoatrial node dysfunction and deafness, MIM# 614896; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7716 CACNA1H Zornitza Stark Gene: cacna1h has been classified as Green List (High Evidence).
Mendeliome v0.7716 CACNA1H Zornitza Stark Phenotypes for gene: CACNA1H were changed from to Hyperaldosteronism, familial, type IV MIM#617027; MONDO:0014875
Mendeliome v0.7715 CACNA1H Zornitza Stark Publications for gene: CACNA1H were set to
Mendeliome v0.7714 CACNA1H Zornitza Stark Mode of inheritance for gene: CACNA1H was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7713 CACNA1H Zornitza Stark reviewed gene: CACNA1H: Rating: GREEN; Mode of pathogenicity: None; Publications: 27729216, 25907736, 31126930; Phenotypes: Hyperaldosteronism, familial, type IV MIM#617027, MONDO:0014875; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7713 COX16 Zornitza Stark Phenotypes for gene: COX16 were changed from Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis to Mitochondrial complex IV deficiency, nuclear type 22, MIM# 619355; Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis
Mendeliome v0.7712 COX16 Zornitza Stark reviewed gene: COX16: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 22, MIM# 619355; Mode of inheritance: None
Mendeliome v0.7712 NSF Zornitza Stark Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, MIM# 619340; Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Mendeliome v0.7711 NSF Zornitza Stark edited their review of gene: NSF: Changed phenotypes: Developmental and epileptic encephalopathy 96, MIM# 619340, Seizures, EEG with burst suppression, Global developmental delay, Intellectual disability
Mendeliome v0.7711 IPO8 Zornitza Stark Publications for gene: IPO8 were set to
Mendeliome v0.7710 IPO8 Zornitza Stark Classified gene: IPO8 as Green List (high evidence)
Mendeliome v0.7710 IPO8 Zornitza Stark Gene: ipo8 has been classified as Green List (High Evidence).
Mendeliome v0.7709 IPO8 Zornitza Stark edited their review of gene: IPO8: Changed rating: GREEN; Changed publications: 34010604
Mendeliome v0.7709 NFU1 Zornitza Stark Gene: nfu1 has been classified as Green List (High Evidence).
Mendeliome v0.7709 NFU1 Zornitza Stark Phenotypes for gene: NFU1 were changed from to Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711
Mendeliome v0.7708 NFU1 Zornitza Stark Publications for gene: NFU1 were set to
Mendeliome v0.7707 NFU1 Zornitza Stark Mode of inheritance for gene: NFU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7706 NFU1 Zornitza Stark reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21944046, 22077971, 32747156, 29441221; Phenotypes: Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7706 RAB11B Zornitza Stark commented on gene: RAB11B: NDAGSCW is a neurodevelopmental disorder characterized by severely delayed psychomotor development apparent from infancy. Affected individuals have delayed and difficulty walking, intellectual disability, absent speech, and variable additional features, including hip dysplasia, tapering fingers, and seizures. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem.
Mendeliome v0.7706 RAB11B Zornitza Stark Gene: rab11b has been classified as Green List (High Evidence).
Mendeliome v0.7706 RAB11B Zornitza Stark Phenotypes for gene: RAB11B were changed from to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 617807
Mendeliome v0.7705 RAB11B Zornitza Stark Publications for gene: RAB11B were set to
Mendeliome v0.7704 RAB11B Zornitza Stark Mode of inheritance for gene: RAB11B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7703 RAB11B Zornitza Stark reviewed gene: RAB11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29106825; Phenotypes: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 617807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7703 UFSP2 Zornitza Stark Gene: ufsp2 has been classified as Green List (High Evidence).
Mendeliome v0.7703 UFSP2 Zornitza Stark Phenotypes for gene: UFSP2 were changed from to Neurodevelopmental disorder; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v0.7702 UFSP2 Zornitza Stark Publications for gene: UFSP2 were set to
Mendeliome v0.7701 UFSP2 Zornitza Stark Mode of inheritance for gene: UFSP2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7700 UFSP2 Zornitza Stark changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all. Additional cases identified through the 100,000 Genomes project.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.
Mendeliome v0.7700 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Changed rating: GREEN
Mendeliome v0.7700 KLHL13 Zornitza Stark Gene: klhl13 has been classified as Red List (Low Evidence).
Mendeliome v0.7700 KLHL13 Zornitza Stark gene: KLHL13 was added
gene: KLHL13 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLHL13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL13 were set to 24627108
Phenotypes for gene: KLHL13 were set to HMSN
Review for gene: KLHL13 was set to RED
Added comment: Single family (two affected males) with an inherited peripheral neuropathy, no functional analysis.
Sources: Expert Review
Mendeliome v0.7699 PRX Zornitza Stark Gene: prx has been classified as Green List (High Evidence).
Mendeliome v0.7699 PRX Zornitza Stark Phenotypes for gene: PRX were changed from to Charcot-Marie-Tooth disease, type 4F, MIM# 614895; Dejerine-Sottas disease, MIM# 145900
Mendeliome v0.7698 PRX Zornitza Stark Publications for gene: PRX were set to
Mendeliome v0.7697 PRX Zornitza Stark Mode of inheritance for gene: PRX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7696 PRX Zornitza Stark reviewed gene: PRX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11133365, 11157804, 15197604, 21079185, 22847150, 10839370, 32460404, 31523542, 31426691; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM# 614895, Dejerine-Sottas disease, MIM# 145900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Gene: plekhg5 has been classified as Green List (High Evidence).
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Phenotypes for gene: PLEKHG5 were changed from to Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376; Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067
Mendeliome v0.7695 PLEKHG5 Zornitza Stark Publications for gene: PLEKHG5 were set to
Mendeliome v0.7694 PLEKHG5 Zornitza Stark Mode of inheritance for gene: PLEKHG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7693 PLEKHG5 Zornitza Stark reviewed gene: PLEKHG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564964, 23777631, 23844677, 33492783, 33275839, 33220101, 23777631; Phenotypes: Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376, Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7693 NEFL Zornitza Stark Gene: nefl has been classified as Green List (High Evidence).
Mendeliome v0.7693 NEFL Zornitza Stark Phenotypes for gene: NEFL were changed from to Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882; Charcot-Marie-Tooth disease, type 1F, MIM# 607734; Charcot-Marie-Tooth disease, type 2E 607684
Mendeliome v0.7692 NEFL Zornitza Stark Publications for gene: NEFL were set to
Mendeliome v0.7691 NEFL Zornitza Stark Mode of inheritance for gene: NEFL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7690 NEFL Zornitza Stark reviewed gene: NEFL: Rating: GREEN; Mode of pathogenicity: None; Publications: 10841809, 12393795, 14733962, 24887401, 25877835, 20039262, 12566280, 29191368, 28902413; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate G, MIM# 617882, Charcot-Marie-Tooth disease, type 1F, MIM# 607734, Charcot-Marie-Tooth disease, type 2E 607684; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7690 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Mendeliome v0.7690 ADNP Zornitza Stark Phenotypes for gene: ADNP were changed from to Helsmoortel-van der Aa syndrome MIM#615873; MONDO:0014379
Mendeliome v0.7689 ADNP Zornitza Stark Publications for gene: ADNP were set to
Mendeliome v0.7688 ADNP Zornitza Stark Mode of inheritance for gene: ADNP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7687 ADNP Zornitza Stark reviewed gene: ADNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 24531329, 25057125, 25533962, 29724491; Phenotypes: Helsmoortel-van der Aa syndrome MIM#615873, MONDO:0014379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7687 ADNP Elena Savva reviewed gene: ADNP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29911927; Phenotypes: Helsmoortel-van der Aa syndrome MIM#615873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7687 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7687 CHUK Zornitza Stark Phenotypes for gene: CHUK were changed from to Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome
Mendeliome v0.7686 CHUK Zornitza Stark Publications for gene: CHUK were set to
Mendeliome v0.7685 CHUK Zornitza Stark Mode of inheritance for gene: CHUK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7684 CHUK Zornitza Stark Classified gene: CHUK as Amber List (moderate evidence)
Mendeliome v0.7684 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7683 CHUK Zornitza Stark reviewed gene: CHUK: Rating: AMBER; Mode of pathogenicity: None; Publications: 25691407, 20961246, 10195895, 10195896, 29523099, 28513979; Phenotypes: Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339, Cocoon syndrome, MIM# 613630, AEC-like syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7683 TMEM251 Zornitza Stark Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type 619345
Mendeliome v0.7682 TMEM251 Zornitza Stark reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysostosis multiplex, Ain-Naz type 619345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7682 PARP6 Zornitza Stark Mode of inheritance for gene: PARP6 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7681 PARP6 Zornitza Stark edited their review of gene: PARP6: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7681 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7680 PARP6 Zornitza Stark gene: PARP6 was added
gene: PARP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PARP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Gene: mapkbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Phenotypes for gene: MAPKBP1 were changed from to Nephronophthisis 20, MIM# 617271; MONDO:0014997
Mendeliome v0.7678 MAPKBP1 Zornitza Stark Publications for gene: MAPKBP1 were set to
Mendeliome v0.7677 MAPKBP1 Zornitza Stark Mode of inheritance for gene: MAPKBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7676 MAPKBP1 Zornitza Stark reviewed gene: MAPKBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28089251, 33623699, 32505465, 32055034; Phenotypes: Nephronophthisis 20, MIM# 617271, MONDO:0014997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7676 SLC6A6 Zornitza Stark Phenotypes for gene: SLC6A6 were changed from Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy
Mendeliome v0.7675 DNAJB2 Zornitza Stark Gene: dnajb2 has been classified as Green List (High Evidence).
Mendeliome v0.7675 DNAJB2 Zornitza Stark Phenotypes for gene: DNAJB2 were changed from to Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881; MONDO:0014866
Mendeliome v0.7674 DNAJB2 Zornitza Stark Publications for gene: DNAJB2 were set to
Mendeliome v0.7673 DNAJB2 Zornitza Stark Mode of inheritance for gene: DNAJB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7672 DNAJB2 Zornitza Stark reviewed gene: DNAJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522442, 25274842, 33369814, 22522442; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881, MONDO:0014866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7672 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489 to Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; Spinal muscular atrophy, distal, X-linked 3, MIM# 300489
Mendeliome v0.7671 ATP7A Zornitza Stark Publications for gene: ATP7A were set to 21221114
Mendeliome v0.7670 ATP7A Zornitza Stark reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170900, 33137485, 31969342, 31558336; Phenotypes: Menkes disease MIM#309400, Occipital horn syndrome MIM#304150, Spinal muscular atrophy, distal, X-linked 3, MIM# 300489; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7670 UFSP2 Zornitza Stark changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: single 3-generation family reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.
Mendeliome v0.7670 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Changed publications: 33473208, 26428751, 28892125, 32755715
Mendeliome v0.7670 UFSP2 Zornitza Stark reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33473208, 26428751, 28892125; Phenotypes: Neurodevelopmental disorder, Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7670 TRPV6 Zornitza Stark Marked gene: TRPV6 as ready
Mendeliome v0.7670 TRPV6 Zornitza Stark Gene: trpv6 has been classified as Green List (High Evidence).
Mendeliome v0.7670 TRPV6 Zornitza Stark Phenotypes for gene: TRPV6 were changed from to Hyperparathyroidism, transient neonatal, MIM# 618188; Early onset chronic pancreatitis susceptibility
Mendeliome v0.7669 TRPV6 Zornitza Stark Publications for gene: TRPV6 were set to
Mendeliome v0.7668 TRPV6 Zornitza Stark Mode of inheritance for gene: TRPV6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7667 TRPV6 Zornitza Stark reviewed gene: TRPV6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32383311, 31930989, 29861107; Phenotypes: Hyperparathyroidism, transient neonatal, MIM# 618188, Early onset chronic pancreatitis susceptibility; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7667 FAR1 Zornitza Stark Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; spastic paraparesis and bilateral cataracts to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338
Mendeliome v0.7666 FAR1 Zornitza Stark edited their review of gene: FAR1: Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, Cataracts, spastic paraparesis, and speech delay, MIM#619338
Mendeliome v0.7666 CLDN11 Zornitza Stark Phenotypes for gene: CLDN11 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy-22, MIM#619328
Mendeliome v0.7665 CLDN11 Zornitza Stark reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomyelinating leukodystrophy-22, MIM#619328; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7665 BICRA Zornitza Stark Phenotypes for gene: BICRA were changed from Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features to Coffin-Siris syndrome-12, MIM#619325; Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features
Mendeliome v0.7664 BICRA Zornitza Stark reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7664 RETREG1 Zornitza Stark Marked gene: RETREG1 as ready
Mendeliome v0.7664 RETREG1 Zornitza Stark Gene: retreg1 has been classified as Green List (High Evidence).
Mendeliome v0.7664 RETREG1 Zornitza Stark Phenotypes for gene: RETREG1 were changed from to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; MONDO:0013142
Mendeliome v0.7663 RETREG1 Zornitza Stark Publications for gene: RETREG1 were set to
Mendeliome v0.7662 RETREG1 Zornitza Stark Mode of inheritance for gene: RETREG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7661 RETREG1 Zornitza Stark reviewed gene: RETREG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19838196, 24327336, 31737055, 31596031; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115, MONDO:0013142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7661 SBF1 Zornitza Stark Gene: sbf1 has been classified as Green List (High Evidence).
Mendeliome v0.7661 SBF1 Zornitza Stark Phenotypes for gene: SBF1 were changed from to Charcot-Marie-Tooth disease, type 4B3 , MIM#615284; MONDO:0014117
Mendeliome v0.7660 SBF1 Zornitza Stark Publications for gene: SBF1 were set to
Mendeliome v0.7659 SBF1 Zornitza Stark Mode of inheritance for gene: SBF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7658 SBF1 Zornitza Stark reviewed gene: SBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23749797, 23749797, 32444983, 30039846, 28005197; Phenotypes: Charcot-Marie-Tooth disease, type 4B3 , MIM#615284, MONDO:0014117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7658 SBF2 Zornitza Stark Gene: sbf2 has been classified as Green List (High Evidence).
Mendeliome v0.7658 SBF2 Zornitza Stark Phenotypes for gene: SBF2 were changed from to Charcot-Marie-Tooth disease, type 4B2 , MIM#604563
Mendeliome v0.7657 SBF2 Zornitza Stark Publications for gene: SBF2 were set to
Mendeliome v0.7656 SBF2 Zornitza Stark Mode of inheritance for gene: SBF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7655 SBF2 Zornitza Stark reviewed gene: SBF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12554688, 15477569, 12687498, 15304601, 31772832, 31070812; Phenotypes: Charcot-Marie-Tooth disease, type 4B2 , MIM#604563; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7655 SCN10A Zornitza Stark Gene: scn10a has been classified as Green List (High Evidence).
Mendeliome v0.7655 SCN10A Zornitza Stark Phenotypes for gene: SCN10A were changed from to Episodic pain syndrome, familial, 2, MIM# 615551
Mendeliome v0.7654 SCN10A Zornitza Stark Publications for gene: SCN10A were set to
Mendeliome v0.7653 SCN10A Zornitza Stark Mode of inheritance for gene: SCN10A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7652 SCN10A Zornitza Stark reviewed gene: SCN10A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23115331, 33775738, 30731422, 30554136; Phenotypes: Episodic pain syndrome, familial, 2, MIM# 615551; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7652 KCNA2 Elena Savva reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33802230, 29050392; Phenotypes: Developmental and epileptic encephalopathy 32, MIM#616366; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7652 MYCN Kristin Rigbye reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21224895, 8470948; Phenotypes: Feingold syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7652 TBC1D2B Zornitza Stark Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth (NEDSGO), MIM#619323; Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Mendeliome v0.7651 TBC1D2B Zornitza Stark edited their review of gene: TBC1D2B: Changed phenotypes: Neurodevelopmental disorder with seizures and gingival overgrowth (NEDSGO), MIM#619323, Global developmental delay, Intellectual disability, Seizures, Gingival overgrowth, Behavioral abnormality, Abnormality of the mandible, Abnormality of brain morphology, Abnormality of the eye, Hearing abnormality
Mendeliome v0.7651 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Green List (High Evidence).
Mendeliome v0.7651 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000; Fibromuscular dysplasia, multifocal, MIM# 619329
Mendeliome v0.7650 COL5A1 Zornitza Stark Publications for gene: COL5A1 were set to
Mendeliome v0.7649 COL5A1 Zornitza Stark Mode of inheritance for gene: COL5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7648 COL5A1 Zornitza Stark reviewed gene: COL5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 32938213; Phenotypes: Ehlers-Danlos syndrome, classic type, 1, MIM# 130000, Fibromuscular dysplasia, multifocal, MIM# 619329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7648 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Developmental and epileptic encephalopathy 6B, non-Dravet, MIM# 619317; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita
Mendeliome v0.7647 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208, Developmental and epileptic encephalopathy 6B, non-Dravet, MIM# 619317, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures, Arthrogryposis multiplex congenita
Mendeliome v0.7647 KDM4B Zornitza Stark Phenotypes for gene: KDM4B were changed from Global developmental delay, intellectual disability and neuroanatomical defects to Intellectual developmental disorder, autosomal dominant 65, MIM# 619320; Global developmental delay, intellectual disability and neuroanatomical defects
Mendeliome v0.7646 KDM4B Zornitza Stark reviewed gene: KDM4B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 65, MIM# 619320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7646 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Mendeliome v0.7646 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from to Dyskeratosis congenita, X-linked 305000; Hoyeraal-Hreidarsson Syndrome
Mendeliome v0.7645 DKC1 Zornitza Stark Publications for gene: DKC1 were set to
Mendeliome v0.7644 DKC1 Zornitza Stark Mode of inheritance for gene: DKC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7643 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31269755, 26951492, 29081935, 25940403; Phenotypes: Dyskeratosis congenita, X-linked 305000, Hoyeraal-Hreidarsson Syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7643 THOC2 Zornitza Stark Marked gene: THOC2 as ready
Mendeliome v0.7643 THOC2 Zornitza Stark Gene: thoc2 has been classified as Green List (High Evidence).
Mendeliome v0.7643 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from to Mental retardation, X-linked 12/35 MIM#300957
Mendeliome v0.7642 THOC2 Zornitza Stark Publications for gene: THOC2 were set to
Mendeliome v0.7641 THOC2 Zornitza Stark Mode of inheritance for gene: THOC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7640 FGA Zornitza Stark Gene: fga has been classified as Green List (High Evidence).
Mendeliome v0.7640 FGA Zornitza Stark Phenotypes for gene: FGA were changed from to Afibrinogenemia, congenital (MIM#202400), AR; Amyloidosis, familial visceral (MIM#105200), AD
Mendeliome v0.7639 FGA Zornitza Stark Publications for gene: FGA were set to
Mendeliome v0.7638 FGA Zornitza Stark Mode of inheritance for gene: FGA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7637 THOC2 Paul De Fazio changed review comment from: Multiple (>10) individuals with neurodevelopmental phenotypes reported with missense, splice, and exon deletion variants. Variants are reported de novo or inherited from a carrier mother. Note that null (whole gene deletion or NMD) variants have not been reported in affected individuals. Arg77Cys appears to be recurrent (reported in multiple individuals).; to: Multiple (>10) males with neurodevelopmental phenotypes reported with missense, splice, and exon deletion variants. Variants are reported de novo or inherited from a carrier mother. Note that null (whole gene deletion or NMD) variants have not been reported in affected individuals. Arg77Cys appears to be recurrent (reported in multiple individuals).
Mendeliome v0.7637 THOC2 Paul De Fazio edited their review of gene: THOC2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7637 THOC2 Paul De Fazio reviewed gene: THOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26166480, 32116545, 29851191, 32960281; Phenotypes: Mental retardation, X-linked 12/35 MIM#300957; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.7637 FGA Chern Lim reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31064749, 17295221, 19073821, 11739173; Phenotypes: Afibrinogenemia, congenital (MIM#202400), AR, Amyloidosis, familial visceral (MIM#105200), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7637 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Green List (High Evidence).
Mendeliome v0.7637 GRHL2 Zornitza Stark Phenotypes for gene: GRHL2 were changed from to Ectodermal dysplasia/short stature syndrome MIM#616029; Corneal dystrophy, posterior polymorphous, 4, MIM# 618031; Deafness, autosomal dominant 28, MIM# 608641
Mendeliome v0.7636 GRHL2 Zornitza Stark Publications for gene: GRHL2 were set to
Mendeliome v0.7635 GRHL2 Zornitza Stark Mode of inheritance for gene: GRHL2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7634 GRHL2 Zornitza Stark reviewed gene: GRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25152456, 29499165; Phenotypes: Ectodermal dysplasia/short stature syndrome MIM#616029, Corneal dystrophy, posterior polymorphous, 4, MIM# 618031, Deafness, autosomal dominant 28, MIM# 608641; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7634 ST14 Zornitza Stark Marked gene: ST14 as ready
Mendeliome v0.7634 ST14 Zornitza Stark Gene: st14 has been classified as Green List (High Evidence).
Mendeliome v0.7634 ST14 Zornitza Stark Phenotypes for gene: ST14 were changed from to Ichthyosis, congenital, autosomal recessive 11, MIM# MIM#602400
Mendeliome v0.7633 ST14 Zornitza Stark Publications for gene: ST14 were set to
Mendeliome v0.7632 ST14 Zornitza Stark Mode of inheritance for gene: ST14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7631 ST14 Zornitza Stark reviewed gene: ST14: Rating: GREEN; Mode of pathogenicity: None; Publications: 18843291, 29611532, 17273967; Phenotypes: Ichthyosis, congenital, autosomal recessive 11 MIM#602400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7631 CPE Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7631 CPE Zornitza Stark Classified gene: CPE as Amber List (moderate evidence)
Mendeliome v0.7631 CPE Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7630 CPE Zornitza Stark gene: CPE was added
gene: CPE was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Review for gene: CPE was set to AMBER
Added comment: Four affected individuals from two unrelated families reported, bi-allelic LoF variants.
Sources: Expert Review
Mendeliome v0.7629 CELSR1 Zornitza Stark Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v0.7629 CELSR1 Zornitza Stark Classified gene: CELSR1 as Green List (high evidence)
Mendeliome v0.7629 CELSR1 Zornitza Stark Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v0.7628 CELSR1 Zornitza Stark gene: CELSR1 was added
gene: CELSR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770
Phenotypes for gene: CELSR1 were set to Lymphatic malformation 9, MIM# 619319
Review for gene: CELSR1 was set to GREEN
Added comment: 3 unrelated families reported.
Sources: Literature
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Classified gene: SLC2A4RG as Red List (low evidence)
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7626 SLCO1B1 Zornitza Stark Added comment: Comment when marking as ready: Not a monogenic disorder.
Mendeliome v0.7626 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Red List (Low Evidence).
Mendeliome v0.7626 SLCO1B1 Zornitza Stark Phenotypes for gene: SLCO1B1 were changed from to Hyperbilirubinemia, Rotor type, digenic 237450
Mendeliome v0.7625 SLCO1B1 Zornitza Stark Publications for gene: SLCO1B1 were set to
Mendeliome v0.7624 SLCO1B1 Zornitza Stark Classified gene: SLCO1B1 as Red List (low evidence)
Mendeliome v0.7624 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Red List (Low Evidence).
Mendeliome v0.7623 SLC2A4RG Melanie Marty reviewed gene: SLC2A4RG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.7623 SLCO1B1 Dean Phelan reviewed gene: SLCO1B1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30250148, 24918167; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7623 SIAH1 Zornitza Stark Phenotypes for gene: SIAH1 were changed from Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia to Buratti-Harel syndrome, MIM# 619314; Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia
Mendeliome v0.7622 SIAH1 Zornitza Stark reviewed gene: SIAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Buratti-Harel syndrome, MIM# 619314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7622 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Mendeliome v0.7622 SMARCA5 Zornitza Stark Classified gene: SMARCA5 as Green List (high evidence)
Mendeliome v0.7622 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Mendeliome v0.7621 SMARCA5 Zornitza Stark gene: SMARCA5 was added
gene: SMARCA5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMARCA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA5 were set to 33980485
Phenotypes for gene: SMARCA5 were set to Neurodevelopmental disorder; microcephaly; dysmorphic features
Review for gene: SMARCA5 was set to GREEN
Added comment: 12 individuals reported with either de novo or appropriately segregating variants in this gene and mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Functional data supports gene-disease association.
Sources: Literature
Mendeliome v0.7620 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from Developmental disorder to FBXW7-related neurodevelopmental syndrome
Mendeliome v0.7619 FBXW7 Zornitza Stark Classified gene: FBXW7 as Green List (high evidence)
Mendeliome v0.7619 FBXW7 Zornitza Stark Gene: fbxw7 has been classified as Green List (High Evidence).
Mendeliome v0.7618 FBXW7 Elena Savva reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33057194; Phenotypes: FBXW7-related neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7618 LEMD2 Zornitza Stark changed review comment from: Recurrent de novo variant in both individuals; to: Recurrent de novo variant in both individuals p.Ser479Phe.
Mendeliome v0.7618 LEMD2 Zornitza Stark Phenotypes for gene: LEMD2 were changed from progeroid disorder to Marbach-Rustad progeroid syndrome, OMIM# 619322; progeroid disorder
Mendeliome v0.7617 LEMD2 Zornitza Stark reviewed gene: LEMD2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Marbach-Rustad progeroid syndrome, OMIM# 619322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7617 SEPT9 Zornitza Stark Publications for gene: SEPT9 were set to
Mendeliome v0.7616 SEPT9 Zornitza Stark Mode of inheritance for gene: SEPT9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7615 SEPT9 Zornitza Stark Tag SV/CNV tag was added to gene: SEPT9.
Tag 5'UTR tag was added to gene: SEPT9.
Tag founder tag was added to gene: SEPT9.
Tag new gene name tag was added to gene: SEPT9.
Mendeliome v0.7615 SEPT9 Zornitza Stark edited their review of gene: SEPT9: Added comment: Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant form of recurrent focal neuropathy characterized clinically by acute, recurrent episodes of brachial plexus neuropathy with muscle weakness and atrophy preceded by severe pain in the affected arm. Multiple founder variants, including p.Arg88Trp. Also note intragenic duplication and 5'UTR variant reported, which may not be detectable by all NGS assays.; Changed publications: 16186812, 19451530, 19939853, 19139049
Mendeliome v0.7615 SLC5A7 Zornitza Stark Gene: slc5a7 has been classified as Green List (High Evidence).
Mendeliome v0.7615 SLC5A7 Zornitza Stark Phenotypes for gene: SLC5A7 were changed from to Neuronopathy, distal hereditary motor, type VIIA, MIM# 158580; MONDO:0008024; Myasthenic syndrome, congenital, 20, presynaptic, MIM# 617143
Mendeliome v0.7614 SLC5A7 Zornitza Stark Publications for gene: SLC5A7 were set to
Mendeliome v0.7613 SLC5A7 Zornitza Stark Mode of inheritance for gene: SLC5A7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7612 SLC5A7 Zornitza Stark reviewed gene: SLC5A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23141292, 15173594, 29782645, 29582019, 27569547, 29189923, 30172469; Phenotypes: Neuronopathy, distal hereditary motor, type VIIA, MIM# 158580, MONDO:0008024, Myasthenic syndrome, congenital, 20, presynaptic, MIM# 617143; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7612 SMN1 Zornitza Stark changed review comment from: Well established gene-disease association. Deletions common.; to: Well established gene-disease association. Deletions common. High sequence homology between SMN1 and SMN2 can make NGS data difficult to interpret.
Mendeliome v0.7612 MCM10 Zornitza Stark Phenotypes for gene: MCM10 were changed from Susceptibility to CMV; Restrictive cardiomyopathy to Immunodeficiency-80 with or without congenital cardiomyopathy (IMD80), MIM#619313; Susceptibility to CMV; Restrictive cardiomyopathy
Mendeliome v0.7611 MCM10 Zornitza Stark edited their review of gene: MCM10: Changed phenotypes: Immunodeficiency-80 with or without congenital cardiomyopathy (IMD80), MIM#619313, Susceptibility to CMV, Restrictive cardiomyopathy
Mendeliome v0.7611 NR3C2 Zornitza Stark Gene: nr3c2 has been classified as Green List (High Evidence).
Mendeliome v0.7611 NR3C2 Zornitza Stark Phenotypes for gene: NR3C2 were changed from to Pseudohypoaldosteronism type I, autosomal dominant, MIM# 177735; MONDO:0008329
Mendeliome v0.7610 NR3C2 Zornitza Stark Publications for gene: NR3C2 were set to
Mendeliome v0.7609 NR3C2 Zornitza Stark Mode of inheritance for gene: NR3C2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7608 NR3C2 Zornitza Stark reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9662404, 11134129, 11344206, 12788847, 16972228; Phenotypes: Pseudohypoaldosteronism type I, autosomal dominant, MIM# 177735, MONDO:0008329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7608 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Mendeliome v0.7608 SCNN1A Zornitza Stark Phenotypes for gene: SCNN1A were changed from to Liddle syndrome 3 618126, MIM# AD, MONDO:0029132; Bronchiectasis with or without elevated sweat chloride 2, MIM# 613021 AD, MONDO:0013087; Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917
Mendeliome v0.7607 SCNN1A Zornitza Stark Publications for gene: SCNN1A were set to
Mendeliome v0.7606 SCNN1A Zornitza Stark Mode of inheritance for gene: SCNN1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7605 SCNN1A Zornitza Stark reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31301676, 28710092, 19462466, 19017867; Phenotypes: Liddle syndrome 3 618126, MIM# AD, MONDO:0029132, Bronchiectasis with or without elevated sweat chloride 2, MIM# 613021 AD, MONDO:0013087, Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7605 SPTLC1 Zornitza Stark Marked gene: SPTLC1 as ready
Mendeliome v0.7605 SPTLC1 Zornitza Stark Gene: sptlc1 has been classified as Green List (High Evidence).
Mendeliome v0.7605 SPTLC1 Zornitza Stark Phenotypes for gene: SPTLC1 were changed from to Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.7604 SPTLC1 Zornitza Stark Publications for gene: SPTLC1 were set to
Mendeliome v0.7603 SPTLC1 Zornitza Stark Mode of inheritance for gene: SPTLC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7602 SPTLC2 Zornitza Stark Marked gene: SPTLC2 as ready
Mendeliome v0.7602 SPTLC2 Zornitza Stark Gene: sptlc2 has been classified as Green List (High Evidence).
Mendeliome v0.7602 SPTLC2 Zornitza Stark Phenotypes for gene: SPTLC2 were changed from to Neuropathy, hereditary sensory and autonomic, type IC, 613640; MONDO:0013337; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.7601 SPTLC2 Zornitza Stark Publications for gene: SPTLC2 were set to
Mendeliome v0.7600 SPTLC2 Zornitza Stark Mode of inheritance for gene: SPTLC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7599 ZPR1 Zornitza Stark Tag founder tag was added to gene: ZPR1.
Mendeliome v0.7599 ZPR1 Zornitza Stark Gene: zpr1 has been classified as Red List (Low Evidence).
Mendeliome v0.7599 ZPR1 Zornitza Stark gene: ZPR1 was added
gene: ZPR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to Growth restriction, hypoplastic kidneys, alpecia, and distinctive facies 619321
Review for gene: ZPR1 was set to RED
Added comment: 3 families reported with growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF). All were Hispanic families from the middle Rio Grande Valley. Homozygous missense identified in one family, p. Ile196Thr. Others unavailable for testing, founder effect postulated.
Sources: Literature
Mendeliome v0.7598 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Mendeliome v0.7598 SPEN Zornitza Stark Phenotypes for gene: SPEN were changed from Intellectual disability; autism; congenital anomalies to Radio-Tartaglia syndrome, MIM# 619312; Intellectual disability; autism; congenital anomalies
Mendeliome v0.7597 SPEN Zornitza Stark Publications for gene: SPEN were set to 33057194
Mendeliome v0.7596 SPEN Zornitza Stark reviewed gene: SPEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Radio-Tartaglia syndrome, MIM# 619312; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7596 AFF3 Zornitza Stark Gene: aff3 has been classified as Green List (High Evidence).
Mendeliome v0.7596 AFF3 Zornitza Stark Phenotypes for gene: AFF3 were changed from to KINSSHIP syndrome, MIM# 619297
Mendeliome v0.7595 AFF3 Zornitza Stark Publications for gene: AFF3 were set to
Mendeliome v0.7594 AFF3 Zornitza Stark Mode of inheritance for gene: AFF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7593 AFF3 Zornitza Stark reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31388108, 33961779; Phenotypes: KINSSHIP syndrome, MIM# 619297; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7593 KDR Zornitza Stark Gene: kdr has been classified as Green List (High Evidence).
Mendeliome v0.7593 KDR Zornitza Stark Phenotypes for gene: KDR were changed from to Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089
Mendeliome v0.7592 KDR Zornitza Stark Publications for gene: KDR were set to
Mendeliome v0.7591 KDR Zornitza Stark Mode of inheritance for gene: KDR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7590 KDR Zornitza Stark reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31980491, 29650961, 18931684; Phenotypes: Pulmonary hypertension, Haemangioma, capillary infantile, somatic 602089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7590 TRIM2 Zornitza Stark Marked gene: TRIM2 as ready
Mendeliome v0.7590 TRIM2 Zornitza Stark Gene: trim2 has been classified as Green List (High Evidence).
Mendeliome v0.7590 TRIM2 Zornitza Stark Phenotypes for gene: TRIM2 were changed from to Charcot-Marie-Tooth disease, type 2R, MIM# 615490; MONDO:0014208
Mendeliome v0.7589 TRIM2 Zornitza Stark Publications for gene: TRIM2 were set to
Mendeliome v0.7588 TRIM2 Zornitza Stark Mode of inheritance for gene: TRIM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7587 TRIM2 Zornitza Stark reviewed gene: TRIM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562820, 25893792, 18687884, 32815244, 32205255, 25893792; Phenotypes: Charcot-Marie-Tooth disease, type 2R, MIM# 615490, MONDO:0014208; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7587 RAB7A Zornitza Stark Gene: rab7a has been classified as Green List (High Evidence).
Mendeliome v0.7587 RAB7A Zornitza Stark Phenotypes for gene: RAB7A were changed from to Charcot-Marie-Tooth disease, type 2B, MIM# 600882; MONDO:0010949
Mendeliome v0.7586 RAB7A Zornitza Stark Publications for gene: RAB7A were set to
Mendeliome v0.7585 RAB7A Zornitza Stark Mode of inheritance for gene: RAB7A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7584 RAB7A Zornitza Stark reviewed gene: RAB7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 12545426, 17060578, 32326241, 29130394, 25614874; Phenotypes: Charcot-Marie-Tooth disease, type 2B, MIM# 600882, MONDO:0010949; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7584 PRDM12 Zornitza Stark Gene: prdm12 has been classified as Green List (High Evidence).
Mendeliome v0.7584 PRDM12 Zornitza Stark Phenotypes for gene: PRDM12 were changed from to Neuropathy, hereditary sensory and autonomic, type VIII, MIM# 616488; MONDO:0014662
Mendeliome v0.7583 PRDM12 Zornitza Stark Publications for gene: PRDM12 were set to
Mendeliome v0.7582 PRDM12 Zornitza Stark Mode of inheritance for gene: PRDM12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7581 PRDM12 Zornitza Stark reviewed gene: PRDM12: Rating: GREEN; Mode of pathogenicity: None; Publications: 26005867, 33789102, 33010785, 32828702; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VIII, MIM# 616488, MONDO:0014662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7581 FIP1L1 Zornitza Stark Gene: fip1l1 has been classified as Red List (Low Evidence).
Mendeliome v0.7581 FIP1L1 Zornitza Stark Classified gene: FIP1L1 as Red List (low evidence)
Mendeliome v0.7581 FIP1L1 Zornitza Stark Gene: fip1l1 has been classified as Red List (Low Evidence).
Mendeliome v0.7580 FIP1L1 Zornitza Stark reviewed gene: FIP1L1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7580 THBS2 Zornitza Stark Marked gene: THBS2 as ready
Mendeliome v0.7580 THBS2 Zornitza Stark Gene: thbs2 has been classified as Red List (Low Evidence).
Mendeliome v0.7580 THBS2 Zornitza Stark Phenotypes for gene: THBS2 were changed from to {Lumbar disc herniation, susceptibility to} 603932
Mendeliome v0.7579 THBS2 Zornitza Stark Classified gene: THBS2 as Red List (low evidence)
Mendeliome v0.7579 THBS2 Zornitza Stark Gene: thbs2 has been classified as Red List (Low Evidence).
Mendeliome v0.7578 THBS2 Zornitza Stark reviewed gene: THBS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Lumbar disc herniation, susceptibility to} 603932; Mode of inheritance: None
Mendeliome v0.7578 ADIPOQ Zornitza Stark Added comment: Comment when marking as ready: No evidence for association with Mendelian disease.
Mendeliome v0.7578 ADIPOQ Zornitza Stark Gene: adipoq has been classified as Red List (Low Evidence).
Mendeliome v0.7578 ADIPOQ Zornitza Stark Phenotypes for gene: ADIPOQ were changed from to Adiponectin deficiency MIM#612556
Mendeliome v0.7577 ADIPOQ Zornitza Stark Publications for gene: ADIPOQ were set to
Mendeliome v0.7576 ADIPOQ Zornitza Stark Classified gene: ADIPOQ as Red List (low evidence)
Mendeliome v0.7576 ADIPOQ Zornitza Stark Gene: adipoq has been classified as Red List (Low Evidence).
Mendeliome v0.7575 INTU Zornitza Stark Marked gene: INTU as ready
Mendeliome v0.7575 INTU Zornitza Stark Gene: intu has been classified as Green List (High Evidence).
Mendeliome v0.7575 INTU Zornitza Stark Phenotypes for gene: INTU were changed from to ?Orofaciodigital syndrome XVII MIM#617926; ?Short-rib thoracic dysplasia 20 with polydactyly
Mendeliome v0.7574 INTU Zornitza Stark Publications for gene: INTU were set to
Mendeliome v0.7573 INTU Zornitza Stark Mode of inheritance for gene: INTU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7572 ADIPOQ Chern Lim reviewed gene: ADIPOQ: Rating: RED; Mode of pathogenicity: None; Publications: 10918532, 32685557, 33075772, 30574262; Phenotypes: Adiponectin deficiency MIM#612556; Mode of inheritance: None
Mendeliome v0.7572 INTU Elena Savva reviewed gene: INTU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27158779, 29451301, 20067783; Phenotypes: ?Orofaciodigital syndrome XVII MIM#617926, ?Short-rib thoracic dysplasia 20 with polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7572 NGF Zornitza Stark Gene: ngf has been classified as Green List (High Evidence).
Mendeliome v0.7572 NGF Zornitza Stark Phenotypes for gene: NGF were changed from to Neuropathy, hereditary sensory and autonomic, type V, MIM# 608654; MONDO:0012092
Mendeliome v0.7571 NGF Zornitza Stark Publications for gene: NGF were set to
Mendeliome v0.7570 NGF Zornitza Stark Mode of inheritance for gene: NGF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7569 NGF Zornitza Stark reviewed gene: NGF: Rating: GREEN; Mode of pathogenicity: None; Publications: 14976160, 20978020, 33884296, 32693191, 31685654, 30296891; Phenotypes: Neuropathy, hereditary sensory and autonomic, type V, MIM# 608654, MONDO:0012092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7569 SPEG Zornitza Stark Phenotypes for gene: SPEG were changed from Centronuclear myopathy 5, MIM# 615959 to Centronuclear myopathy 5, MIM# 615959; Dilated cardiomyopathy
Mendeliome v0.7568 SPEG Zornitza Stark Publications for gene: SPEG were set to 25087613; 31625632; 30412272; 30157964; 29614691; 29474540; 28624463; 26578207; 25087613
Mendeliome v0.7567 SPEG Zornitza Stark edited their review of gene: SPEG: Added comment: PMIDs 32925938;33794647: Reports of early onset isolated DCM, as well as cardiomyopathy in the context of skeletal myopathy.; Changed publications: 25087613, 31625632, 30412272, 30157964, 29614691, 29474540, 28624463, 26578207, 25087613, 32925938, 33794647; Changed phenotypes: Centronuclear myopathy 5, MIM# 615959, Dilated cardiomyopathy
Mendeliome v0.7567 GREB1L Zornitza Stark changed review comment from: At least 16 families described, and mouse model supports gene-disease association.; to: CAKUT: At least 16 families described, and mouse model supports gene-disease association.
Mendeliome v0.7567 NDUFB3 Zornitza Stark Gene: ndufb3 has been classified as Green List (High Evidence).
Mendeliome v0.7567 NDUFB3 Zornitza Stark Phenotypes for gene: NDUFB3 were changed from to Mitochondrial complex I deficiency, nuclear type 25, MIM# 618246; MONDO:0032629
Mendeliome v0.7566 NDUFB3 Zornitza Stark Publications for gene: NDUFB3 were set to
Mendeliome v0.7565 NDUFB3 Zornitza Stark Mode of inheritance for gene: NDUFB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7564 NDUFB3 Zornitza Stark reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27091925; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, MIM# 618246, MONDO:0032629; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7564 NDUFB3 Elena Savva reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22499348; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, MIM#618246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7564 RALA Zornitza Stark Phenotypes for gene: RALA were changed from Intellectual disability; Seizures to Hiatt-Neu-Cooper neurodevelopmental syndrome, MIM# 619311; Intellectual disability; Seizures
Mendeliome v0.7563 RALA Zornitza Stark edited their review of gene: RALA: Changed phenotypes: Hiatt-Neu-Cooper neurodevelopmental syndrome, MIM# 619311, Intellectual disability, Seizures
Mendeliome v0.7563 EXOSC1 Zornitza Stark Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 1F, MIM# 619304
Mendeliome v0.7562 EXOSC1 Zornitza Stark edited their review of gene: EXOSC1: Changed phenotypes: Pontocerebellar hypoplasia, type 1F, MIM# 619304
Mendeliome v0.7562 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505 to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7561 SLC25A46 Zornitza Stark changed review comment from: 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.; 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. New disease entity added by OMIM in 2021 to reflect this more severe end of the spectrum.

At least 10 unrelated families reported, supportive functional data.
Mendeliome v0.7561 SLC25A46 Zornitza Stark edited their review of gene: SLC25A46: Changed phenotypes: Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7561 CAPN15 Zornitza Stark Phenotypes for gene: CAPN15 were changed from microphthalmia HP:0000568; coloboma HP:0000589 to Oculogastrointestinal neurodevelopmental syndrome, MIM# 619318; microphthalmia HP:0000568; coloboma HP:0000589
Mendeliome v0.7560 CAPN15 Zornitza Stark Publications for gene: CAPN15 were set to 32885237
Mendeliome v0.7559 CAPN15 Zornitza Stark reviewed gene: CAPN15: Rating: GREEN; Mode of pathogenicity: None; Publications: 33410501; Phenotypes: Oculogastrointestinal neurodevelopmental syndrome, MIM# 619318, microphthalmia HP:0000568, coloboma HP:0000589; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7559 EXOC2 Zornitza Stark Phenotypes for gene: EXOC2 were changed from Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology to Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306; Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Mendeliome v0.7558 EXOC2 Zornitza Stark edited their review of gene: EXOC2: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306, Global developmental delay, Intellectual disability, Abnormality of the face, Abnormality of brain morphology
Mendeliome v0.7558 SPI1 Zornitza Stark Gene: spi1 has been classified as Green List (High Evidence).
Mendeliome v0.7558 SPI1 Zornitza Stark Classified gene: SPI1 as Green List (high evidence)
Mendeliome v0.7558 SPI1 Zornitza Stark Gene: spi1 has been classified as Green List (High Evidence).
Mendeliome v0.7557 SPI1 Zornitza Stark gene: SPI1 was added
gene: SPI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPI1 were set to 33951726
Phenotypes for gene: SPI1 were set to Agammaglobulinaemia
Review for gene: SPI1 was set to GREEN
Added comment: Six unrelated individuals reported, four with de novo variants, two unphased. Some functional data.
Sources: Literature
Mendeliome v0.7556 NDRG1 Zornitza Stark Gene: ndrg1 has been classified as Green List (High Evidence).
Mendeliome v0.7556 NDRG1 Zornitza Stark Phenotypes for gene: NDRG1 were changed from to Charcot Marie Tooth disease, type 4D, 601455; MONDO:0011085; Auditory neuropathy
Mendeliome v0.7555 NDRG1 Zornitza Stark Publications for gene: NDRG1 were set to
Mendeliome v0.7554 NDRG1 Zornitza Stark Mode of inheritance for gene: NDRG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7553 NDRG1 Zornitza Stark reviewed gene: NDRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10831399, 24136616, 33334662, 29724652, 29174527, 28776325; Phenotypes: Charcot Marie Tooth disease, type 4D, 601455, MONDO:0011085, Auditory neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7553 MTMR2 Zornitza Stark Marked gene: MTMR2 as ready
Mendeliome v0.7553 MTMR2 Zornitza Stark Gene: mtmr2 has been classified as Green List (High Evidence).
Mendeliome v0.7553 MTMR2 Zornitza Stark Phenotypes for gene: MTMR2 were changed from to Charcot-Marie-Tooth disease, type 4B1, 601382; MONDO:0011066
Mendeliome v0.7552 MTMR2 Zornitza Stark Publications for gene: MTMR2 were set to 10802647; 16249189; 33653949; 32586600; 32488727; 31680794
Mendeliome v0.7552 MTMR2 Zornitza Stark Publications for gene: MTMR2 were set to
Mendeliome v0.7551 MTMR2 Zornitza Stark Mode of inheritance for gene: MTMR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7550 MTMR2 Zornitza Stark reviewed gene: MTMR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802647, 16249189, 33653949, 32586600, 32488727, 31680794; Phenotypes: Charcot-Marie-Tooth disease, type 4B1, 601382, MONDO:0011066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7550 TMEM222 Zornitza Stark Marked gene: TMEM222 as ready
Mendeliome v0.7550 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Mendeliome v0.7550 TMEM222 Zornitza Stark Classified gene: TMEM222 as Green List (high evidence)
Mendeliome v0.7550 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Mendeliome v0.7549 TMEM222 Zornitza Stark gene: TMEM222 was added
gene: TMEM222 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM222 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM222 were set to 33824500
Phenotypes for gene: TMEM222 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: TMEM222 was set to GREEN
Added comment: Polla et al (2021 - PMID: 33824500) report 17 individuals from 9 unrelated families, with biallelic TMEM222 pathogenic variants. The phenotype included motor, speech delay and moderate to severe ID (as universal features). Other manifestations included hypotonia (10/15), broad gait (5/12), seizures (7/17 - belonging to 6/9 families), MRI abnormalities (5/8). Variable behavioral abnormalities were observed (aggressive behavior, shy character, stereotypic movements etc). Abnormal OFC was a feature in several with microcephaly in 7 subjects from 4 families (measurements not available for all 17). Nonspecific facial features were reported in 10/17.
Sources: Literature
Mendeliome v0.7548 CHD5 Zornitza Stark Gene: chd5 has been classified as Green List (High Evidence).
Mendeliome v0.7548 CHD5 Zornitza Stark Classified gene: CHD5 as Green List (high evidence)
Mendeliome v0.7548 CHD5 Zornitza Stark Gene: chd5 has been classified as Green List (High Evidence).
Mendeliome v0.7547 CHD5 Zornitza Stark gene: CHD5 was added
gene: CHD5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD5 were set to 33944996
Phenotypes for gene: CHD5 were set to Intellectual disability; Epilepsy
Review for gene: CHD5 was set to GREEN
Added comment: 16 unrelated individuals reported with language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%).
Sources: Literature
Mendeliome v0.7546 MME Zornitza Stark Gene: mme has been classified as Green List (High Evidence).
Mendeliome v0.7546 MME Zornitza Stark Phenotypes for gene: MME were changed from to Charcot-Marie-Tooth disease, axonal, type 2T, MIM# 617017; MONDO:0014866; Spinocerebellar ataxia 43 MIM#617018
Mendeliome v0.7545 MME Zornitza Stark Publications for gene: MME were set to
Mendeliome v0.7544 MME Zornitza Stark Mode of inheritance for gene: MME was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7543 MME Zornitza Stark reviewed gene: MME: Rating: GREEN; Mode of pathogenicity: None; Publications: 26991897, 27588448, 33144514, 31429185, 27583304; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2T, MIM# 617017, MONDO:0014866, Spinocerebellar ataxia 43 MIM#617018; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7543 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant to Mental retardation, autosomal recessive 45, MIM#615979; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v0.7542 FBXO31 Zornitza Stark Classified gene: FBXO31 as Green List (high evidence)
Mendeliome v0.7542 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Green List (High Evidence).
Mendeliome v0.7541 FBXO31 Zornitza Stark changed review comment from: Single consanguineous family reported with homozygous truncating variant, limited functional evidence.
Sources: Expert list; to: AR intellectual disability: Single consanguineous family reported with homozygous truncating variant, limited functional evidence.
Sources: Expert list
Mendeliome v0.7541 FBXO31 Zornitza Stark edited their review of gene: FBXO31: Added comment: PMIDs 33675180; 32989326: three unrelated individuals with de novo missense variant, (p.Asp334Asn) and spastic-dystonic CP.; Changed rating: GREEN; Changed publications: 24623383, 33675180, 32989326; Changed phenotypes: Mental retardation, autosomal recessive 45, MIM#615979, Spastic-dystonic cerebral palsy, de novo dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7541 RCAN1 Zornitza Stark Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7541 RCAN1 Zornitza Stark Classified gene: RCAN1 as Amber List (moderate evidence)
Mendeliome v0.7541 RCAN1 Zornitza Stark Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7540 RCAN1 Zornitza Stark gene: RCAN1 was added
gene: RCAN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RCAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RCAN1 were set to 33863784
Phenotypes for gene: RCAN1 were set to FSGS; proteinuria
Review for gene: RCAN1 was set to AMBER
Added comment: Two families reported, some functional data.
Sources: Literature
Mendeliome v0.7539 ZNFX1 Zornitza Stark Gene: znfx1 has been classified as Green List (High Evidence).
Mendeliome v0.7539 ZNFX1 Zornitza Stark Phenotypes for gene: ZNFX1 were changed from Multisystem inflammation; susceptibility to viral infections to Multisystem inflammation; susceptibility to viral infections; monocytosis; susceptibility to mycobacterial infection
Mendeliome v0.7538 ZNFX1 Zornitza Stark Classified gene: ZNFX1 as Green List (high evidence)
Mendeliome v0.7538 ZNFX1 Zornitza Stark Gene: znfx1 has been classified as Green List (High Evidence).
Mendeliome v0.7537 ZNFX1 Zornitza Stark gene: ZNFX1 was added
gene: ZNFX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33872655; 33876776
Phenotypes for gene: ZNFX1 were set to Multisystem inflammation; susceptibility to viral infections
Review for gene: ZNFX1 was set to GREEN
Added comment: 15 individuals from 8 families reported with multi-system inflammation and susceptibility to viral infections.

In addition, four indviduals from two unrelated kindreds reported with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis.
Sources: Literature
Mendeliome v0.7536 STXBP3 Zornitza Stark Marked gene: STXBP3 as ready
Mendeliome v0.7536 STXBP3 Zornitza Stark Gene: stxbp3 has been classified as Green List (High Evidence).
Mendeliome v0.7536 STXBP3 Zornitza Stark Classified gene: STXBP3 as Green List (high evidence)
Mendeliome v0.7536 STXBP3 Zornitza Stark Gene: stxbp3 has been classified as Green List (High Evidence).
Mendeliome v0.7535 STXBP3 Zornitza Stark gene: STXBP3 was added
gene: STXBP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: STXBP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STXBP3 were set to 33891011
Phenotypes for gene: STXBP3 were set to Very Early Onset Inflammatory Bowel Disease; Bilateral Sensorineural Hearing Loss; Immune Dysregulation
Review for gene: STXBP3 was set to GREEN
Added comment: 10 individuals from 5 families reported.
Sources: Literature
Mendeliome v0.7534 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
Mendeliome v0.7534 IL21R Zornitza Stark Phenotypes for gene: IL21R were changed from to Immunodeficiency 56, MIM# 615207
Mendeliome v0.7533 IL21R Zornitza Stark Publications for gene: IL21R were set to
Mendeliome v0.7532 IL21R Zornitza Stark Mode of inheritance for gene: IL21R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7531 IL21R Zornitza Stark reviewed gene: IL21R: Rating: GREEN; Mode of pathogenicity: None; Publications: 33929673; Phenotypes: Immunodeficiency 56, MIM# 615207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7531 SCD Zornitza Stark Gene: scd has been classified as Red List (Low Evidence).
Mendeliome v0.7531 SCD Zornitza Stark Classified gene: SCD as Red List (low evidence)
Mendeliome v0.7531 SCD Zornitza Stark Gene: scd has been classified as Red List (Low Evidence).
Mendeliome v0.7530 DPYSL5 Zornitza Stark Gene: dpysl5 has been classified as Green List (High Evidence).
Mendeliome v0.7530 DPYSL5 Zornitza Stark Classified gene: DPYSL5 as Green List (high evidence)
Mendeliome v0.7530 DPYSL5 Zornitza Stark Gene: dpysl5 has been classified as Green List (High Evidence).
Mendeliome v0.7529 SIN3B Zornitza Stark Gene: sin3b has been classified as Green List (High Evidence).
Mendeliome v0.7529 SIN3B Zornitza Stark Mode of inheritance for gene: SIN3B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7528 SIN3B Zornitza Stark Classified gene: SIN3B as Green List (high evidence)
Mendeliome v0.7528 SIN3B Zornitza Stark Gene: sin3b has been classified as Green List (High Evidence).
Mendeliome v0.7527 VPS41 Zornitza Stark Publications for gene: VPS41 were set to 32808683
Mendeliome v0.7526 VPS41 Zornitza Stark Classified gene: VPS41 as Green List (high evidence)
Mendeliome v0.7526 VPS41 Zornitza Stark Gene: vps41 has been classified as Green List (High Evidence).
Mendeliome v0.7525 ANKRD17 Zornitza Stark Publications for gene: ANKRD17 were set to
Mendeliome v0.7524 ANKRD17 Zornitza Stark Classified gene: ANKRD17 as Green List (high evidence)
Mendeliome v0.7524 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Green List (High Evidence).
Mendeliome v0.7523 JAG2 Zornitza Stark Gene: jag2 has been classified as Green List (High Evidence).
Mendeliome v0.7523 JAG2 Zornitza Stark Classified gene: JAG2 as Green List (high evidence)
Mendeliome v0.7523 JAG2 Zornitza Stark Gene: jag2 has been classified as Green List (High Evidence).
Mendeliome v0.7522 NEPRO Zornitza Stark Gene: nepro has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7522 NEPRO Zornitza Stark Classified gene: NEPRO as Amber List (moderate evidence)
Mendeliome v0.7522 NEPRO Zornitza Stark Gene: nepro has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7521 LRSAM1 Zornitza Stark Gene: lrsam1 has been classified as Green List (High Evidence).
Mendeliome v0.7521 LRSAM1 Zornitza Stark Phenotypes for gene: LRSAM1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2P, MIM# 614436; MONDO:0013753
Mendeliome v0.7520 LRSAM1 Zornitza Stark Publications for gene: LRSAM1 were set to
Mendeliome v0.7519 LRSAM1 Zornitza Stark Mode of inheritance for gene: LRSAM1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7518 LRSAM1 Zornitza Stark reviewed gene: LRSAM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20865121, 22012984, 22781092, 27686364, 33568173, 33414056, 30996334; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2P, MIM# 614436, MONDO:0013753; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7518 LITAF Zornitza Stark Marked gene: LITAF as ready
Mendeliome v0.7518 LITAF Zornitza Stark Gene: litaf has been classified as Green List (High Evidence).
Mendeliome v0.7518 LITAF Zornitza Stark Phenotypes for gene: LITAF were changed from to Charcot-Marie-Tooth disease, type 1C, MIM# 601098; MONDO:0010995
Mendeliome v0.7517 LITAF Zornitza Stark Publications for gene: LITAF were set to
Mendeliome v0.7516 LITAF Zornitza Stark Mode of inheritance for gene: LITAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7515 LITAF Zornitza Stark reviewed gene: LITAF: Rating: GREEN; Mode of pathogenicity: None; Publications: 12525712, 19541485, 23359569, 32665875, 28211240; Phenotypes: Charcot-Marie-Tooth disease, type 1C, MIM# 601098, MONDO:0010995; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7515 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Mendeliome v0.7515 SLC3A1 Zornitza Stark Phenotypes for gene: SLC3A1 were changed from to Cystinuria, MIM# 220100
Mendeliome v0.7514 SLC3A1 Zornitza Stark Publications for gene: SLC3A1 were set to
Mendeliome v0.7513 SLC3A1 Zornitza Stark Mode of inheritance for gene: SLC3A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7512 SLC3A1 Zornitza Stark reviewed gene: SLC3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cystinuria, MIM# 220100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7512 LSM7 Bryony Thompson Gene: lsm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7512 LSM7 Bryony Thompson Classified gene: LSM7 as Amber List (moderate evidence)
Mendeliome v0.7512 LSM7 Bryony Thompson Gene: lsm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7511 LSM7 Bryony Thompson gene: LSM7 was added
gene: LSM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LSM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100034
Phenotypes for gene: LSM7 were set to Leukodystrophy; foetal death
Review for gene: LSM7 was set to AMBER
Added comment: Homozygous variant (p.Asp41Asn) identified in a child with leukodystrophy and a homozygous variant (p.Arg69Pro) identified in an individual that died in utero. In vitro and in vivo (zebrafish) assays supporting pathogenicity of the 2 variants.
Sources: Literature
Mendeliome v0.7510 PTPN4 Bryony Thompson Marked gene: PTPN4 as ready
Mendeliome v0.7510 PTPN4 Bryony Thompson Gene: ptpn4 has been classified as Green List (High Evidence).
Mendeliome v0.7510 PTPN4 Bryony Thompson Classified gene: PTPN4 as Green List (high evidence)
Mendeliome v0.7510 PTPN4 Bryony Thompson Gene: ptpn4 has been classified as Green List (High Evidence).
Mendeliome v0.7509 PTPN4 Bryony Thompson gene: PTPN4 was added
gene: PTPN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN4 were set to 17953619; 25424712; 30238967; DOI: https://doi.org/10.1016/j.xhgg.2021.100033
Phenotypes for gene: PTPN4 were set to Intellectual disability; developmental delay
Review for gene: PTPN4 was set to GREEN
Added comment: >3 unrelated probands and supporting mouse model
PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity
PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder
PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines
DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo.
Sources: Literature
Mendeliome v0.7508 SLC3A1 Michelle Torres reviewed gene: SLC3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25964309; Phenotypes: Cystinuria (MIM#220100) AD, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7508 WFS1 Zornitza Stark Publications for gene: WFS1 were set to 25211237
Mendeliome v0.7507 POLR3K Zornitza Stark Tag founder tag was added to gene: POLR3K.
Mendeliome v0.7507 POLR3K Zornitza Stark Gene: polr3k has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7507 POLR3K Zornitza Stark Classified gene: POLR3K as Amber List (moderate evidence)
Mendeliome v0.7507 POLR3K Zornitza Stark Gene: polr3k has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7506 POLR3K Zornitza Stark gene: POLR3K was added
gene: POLR3K was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to 30584594; 33659930
Phenotypes for gene: POLR3K were set to Hypomyelinating leukodystrophy-21, MIM#619310
Review for gene: POLR3K was set to AMBER
Added comment: Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes. Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life.
Sources: Expert Review
Mendeliome v0.7505 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: Wolfram syndrome 1, OMIM:222300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7505 SAG Zornitza Stark Gene: sag has been classified as Green List (High Evidence).
Mendeliome v0.7505 SAG Zornitza Stark Phenotypes for gene: SAG were changed from to Oguchi disease-1, MIM# 258100; Retinitis pigmentosa 47, MIM# 613758
Mendeliome v0.7504 SAG Zornitza Stark Publications for gene: SAG were set to
Mendeliome v0.7503 SAG Zornitza Stark Mode of inheritance for gene: SAG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7502 SAG Zornitza Stark reviewed gene: SAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 7670478, 9565049, 15234147, 28549094, 33047631; Phenotypes: Oguchi disease-1, MIM# 258100, Retinitis pigmentosa 47, MIM# 613758; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7502 YWHAG Zornitza Stark Added comment: Comment when marking as ready: Developmental and epileptic encephalopathy-56 (DEE56) is a neurodevelopmental disorder characterized by early-onset seizures in most patients, followed by impaired intellectual development, variable behavioral abnormalities, and sometimes additional neurologic features, such as ataxia
Mendeliome v0.7502 YWHAG Zornitza Stark Gene: ywhag has been classified as Green List (High Evidence).
Mendeliome v0.7502 YWHAG Zornitza Stark Phenotypes for gene: YWHAG were changed from to Developmental and epileptic encephalopathy 56, (MIMI#617665)
Mendeliome v0.7501 YWHAG Zornitza Stark Publications for gene: YWHAG were set to
Mendeliome v0.7500 YWHAG Zornitza Stark Mode of inheritance for gene: YWHAG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7499 IL6ST Zornitza Stark Publications for gene: IL6ST were set to 28747427; 30309848; 12370259; 16041381; 31914175; 32207811
Mendeliome v0.7498 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Mendeliome v0.7498 OCRL Zornitza Stark Phenotypes for gene: OCRL were changed from to Dent disease 2, MIM# 300555; Lowe syndrome , MIM#309000
Mendeliome v0.7497 OCRL Zornitza Stark Publications for gene: OCRL were set to
Mendeliome v0.7496 OCRL Zornitza Stark Mode of inheritance for gene: OCRL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7495 OCRL Zornitza Stark reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 15627218, 9199559; Phenotypes: Dent disease 2, MIM# 300555, Lowe syndrome , MIM#309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7495 APOL1 Zornitza Stark Phenotypes for gene: APOL1 were changed from {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551 to {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551; {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551
Mendeliome v0.7494 APOL1 Zornitza Stark Publications for gene: APOL1 were set to 29470556; 20647424; 24206458; 20635188
Mendeliome v0.7493 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from Premature aging syndrome, Penttinen type, 601812 to Basal ganglia calcification, idiopathic, 4, MIM# 615007; Kosaki overgrowth syndrome, MIM# 616592; Myeloproliferative disorder with eosinophilia, MIM# 131440; Myofibromatosis, infantile, 1, MIM# 228550; Premature ageing syndrome, Penttinen type, MIM# 601812
Mendeliome v0.7492 PDGFRB Zornitza Stark Publications for gene: PDGFRB were set to 30573803; 26279204
Mendeliome v0.7491 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007, Kosaki overgrowth syndrome, MIM# 616592, Myeloproliferative disorder with eosinophilia, MIM# 131440, Myofibromatosis, infantile, 1, MIM# 228550, Premature ageing syndrome, Penttinen type, MIM# 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7491 YWHAG Ain Roesley reviewed gene: YWHAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 33393734, 33590706, 31926053, 33767733; Phenotypes: Developmental and epileptic encephalopathy 56, (MIMI#617665); Mode of inheritance: None
Mendeliome v0.7491 NEK1 Zornitza Stark Gene: nek1 has been classified as Green List (High Evidence).
Mendeliome v0.7491 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v0.7490 NEK1 Zornitza Stark Publications for gene: NEK1 were set to
Mendeliome v0.7489 NEK1 Zornitza Stark Mode of inheritance for gene: NEK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7488 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7488 IL6ST Eleanor Williams reviewed gene: IL6ST: Rating: ; Mode of pathogenicity: None; Publications: 33517393; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7488 OCRL Eleanor Williams changed review comment from: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.; to: Genotype/Phenotype information:
PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.
Mendeliome v0.7488 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: Lowe syndrome, OMIM:309000; Mode of inheritance: None
Mendeliome v0.7488 APOL1 Eleanor Williams reviewed gene: APOL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33517446; Phenotypes: {Focal Segmental Glomerulosclerosis 4, Susceptibility to} OMIM:612551, {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551; Mode of inheritance: None
Mendeliome v0.7488 PDGFRB Eleanor Williams reviewed gene: PDGFRB: Rating: ; Mode of pathogenicity: None; Publications: 33450762; Phenotypes: Ocular pterygium-digital keloid dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7488 NEK1 Eleanor Williams reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33445179; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7488 INF2 Zornitza Stark Gene: inf2 has been classified as Green List (High Evidence).
Mendeliome v0.7488 INF2 Zornitza Stark Phenotypes for gene: INF2 were changed from to Charcot-Marie-Tooth disease, dominant intermediate E, MIM# 614455; Glomerulosclerosis, focal segmental, 5, MIM# 613237
Mendeliome v0.7487 INF2 Zornitza Stark Publications for gene: INF2 were set to
Mendeliome v0.7486 INF2 Zornitza Stark Mode of inheritance for gene: INF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7485 INF2 Zornitza Stark reviewed gene: INF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22187985, 30680856, 25943269, 20023659; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate E, MIM# 614455, Glomerulosclerosis, focal segmental, 5, MIM# 613237; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7485 MED25 Zornitza Stark changed review comment from: Basel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in mental retardation, as well as variable eye, brain, cardiac, and palatal abnormalities.

7 individuals from 4 families reported initially, founder variant p.Tyr39Cys. Over 20 individuals reported since, including other variants.; to: Basel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in intellectual disability, as well as variable eye, brain, cardiac, and palatal abnormalities.

7 individuals from 4 families reported initially, founder variant p.Tyr39Cys. Over 20 individuals reported since, including other variants.
Mendeliome v0.7485 MED25 Zornitza Stark Gene: med25 has been classified as Green List (High Evidence).
Mendeliome v0.7485 MED25 Zornitza Stark Phenotypes for gene: MED25 were changed from to Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449; Congenital cataract-microcephaly-naevus flammeus syndrome MONDO:0014643
Mendeliome v0.7484 MED25 Zornitza Stark Publications for gene: MED25 were set to
Mendeliome v0.7483 MED25 Zornitza Stark Mode of inheritance for gene: MED25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7482 MED25 Zornitza Stark reviewed gene: MED25: Rating: GREEN; Mode of pathogenicity: None; Publications: 25792360, 32816121; Phenotypes: Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449, Congenital cataract-microcephaly-naevus flammeus syndrome MONDO:0014643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7482 HSPB1 Zornitza Stark Gene: hspb1 has been classified as Green List (High Evidence).
Mendeliome v0.7482 HSPB1 Zornitza Stark Phenotypes for gene: HSPB1 were changed from to Charcot Marie Tooth disease, axonal, type 2F, 606595; MONDO:0011687; Neuropathy, distal hereditary motor, type IIB, 608634; MONDO:0012080
Mendeliome v0.7481 HSPB1 Zornitza Stark Publications for gene: HSPB1 were set to
Mendeliome v0.7480 HSPB1 Zornitza Stark Mode of inheritance for gene: HSPB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7479 HSPB1 Zornitza Stark reviewed gene: HSPB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21785432, 15122254, 18832141, 32639100, 32334137; Phenotypes: Charcot Marie Tooth disease, axonal, type 2F, 606595, MONDO:0011687, Neuropathy, distal hereditary motor, type IIB, 608634, MONDO:0012080; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7479 HINT1 Zornitza Stark Marked gene: HINT1 as ready
Mendeliome v0.7479 HINT1 Zornitza Stark Gene: hint1 has been classified as Green List (High Evidence).
Mendeliome v0.7479 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
Mendeliome v0.7478 HINT1 Zornitza Stark Publications for gene: HINT1 were set to
Mendeliome v0.7477 HINT1 Zornitza Stark Mode of inheritance for gene: HINT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7476 HINT1 Zornitza Stark reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22961002, 33663550, 33404983, 31848916; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7476 GNB4 Zornitza Stark Gene: gnb4 has been classified as Green List (High Evidence).
Mendeliome v0.7476 GNB4 Zornitza Stark Phenotypes for gene: GNB4 were changed from to Charcot-Marie-Tooth disease, dominant intermediate F, MIM# 615185; MONDO:0014074
Mendeliome v0.7475 GNB4 Zornitza Stark Publications for gene: GNB4 were set to
Mendeliome v0.7474 GNB4 Zornitza Stark Mode of inheritance for gene: GNB4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7473 GNB4 Zornitza Stark reviewed gene: GNB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23434117, 28642160, 27908631; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate F, MIM# 615185, MONDO:0014074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7473 GJB1 Zornitza Stark Gene: gjb1 has been classified as Green List (High Evidence).
Mendeliome v0.7473 GJB1 Zornitza Stark Phenotypes for gene: GJB1 were changed from to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800; MONDO:0010549; reversible posterior leukoencephalopathy
Mendeliome v0.7472 GJB1 Zornitza Stark Publications for gene: GJB1 were set to
Mendeliome v0.7471 GJB1 Zornitza Stark Mode of inheritance for gene: GJB1 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 v0.7470 NEPRO Chern Lim gene: NEPRO was added
gene: NEPRO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853
Review for gene: NEPRO was set to AMBER
Added comment: PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant.

PMID 31250547: 1 family with homozygous novel missense

All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies.
Sources: Literature
Mendeliome v0.7470 GJB1 Zornitza Stark reviewed gene: GJB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8266101, 17100997, 17353473, 31842800; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800, MONDO:0010549, reversible posterior leukoencephalopathy; 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 v0.7470 FGD4 Zornitza Stark Gene: fgd4 has been classified as Green List (High Evidence).
Mendeliome v0.7470 FGD4 Zornitza Stark Phenotypes for gene: FGD4 were changed from to Charcot Marie Tooth disease, type 4H, 609311; MONDO:0012250
Mendeliome v0.7469 FGD4 Zornitza Stark Publications for gene: FGD4 were set to
Mendeliome v0.7468 FGD4 Zornitza Stark Mode of inheritance for gene: FGD4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7467 FGD4 Zornitza Stark reviewed gene: FGD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564959, 31152969, 28847448, 28543957; Phenotypes: Charcot Marie Tooth disease, type 4H, 609311, MONDO:0012250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7467 COX6A1 Zornitza Stark Gene: cox6a1 has been classified as Green List (High Evidence).
Mendeliome v0.7467 COX6A1 Zornitza Stark Phenotypes for gene: COX6A1 were changed from to Charcot Marie Tooth disease, recessive intermediate D, MIM# 616039; MONDO:0014467
Mendeliome v0.7466 COX6A1 Zornitza Stark Publications for gene: COX6A1 were set to
Mendeliome v0.7465 COX6A1 Zornitza Stark Mode of inheritance for gene: COX6A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7464 COX6A1 Zornitza Stark reviewed gene: COX6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25152455, 26302975, 25152455; Phenotypes: Charcot Marie Tooth disease, recessive intermediate D, MIM# 616039, MONDO:0014467; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7464 JAG2 Belinda Chong gene: JAG2 was added
gene: JAG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: JAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAG2 were set to PMID: 33861953
Phenotypes for gene: JAG2 were set to muscular dystrophy
Review for gene: JAG2 was set to GREEN
Added comment: Whole-exome sequencing identified 13 families with rare homozygous or compound heterozygous JAG2 variants. Bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy.
Sources: Literature
Mendeliome v0.7464 ANKRD17 Paul De Fazio reviewed gene: ANKRD17: Rating: GREEN; Mode of pathogenicity: None; Publications: 33909992; Phenotypes: Intellectual disability, speech delay, and dysmorphism; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.7464 VPS41 Kristin Rigbye edited their review of gene: VPS41: Changed phenotypes: Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.7464 VPS41 Kristin Rigbye changed review comment from: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function."; to: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function."

"Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia were present in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay. Two siblings further presented with therapy-resistant epilepsy. No major dysmorphic features were found. In two individuals, retinal pigment alterations were noticed. Brain MRI revealed mild cerebellar atrophy and vermian atrophy without other major structural abnormalities in most affected individuals while in one case (Subject 9) bilateral hyperintensities at the nucleus caudatus area were noted. No hearing or vision problems were noted and in cases where nerve conduction studies were performed, these were normal. Transmission electron microscopy (TEM) on peripheral blood lymphocytes from Subject 2 and lymphoblastoid cells from Subject 3 revealed more multilayered vesicles compared to control cells."
Mendeliome v0.7464 SIN3B Elena Savva gene: SIN3B was added
gene: SIN3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIN3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SIN3B were set to PMID: 33811806
Phenotypes for gene: SIN3B were set to Syndromic intellectual disability/autism spectrum disorder
Review for gene: SIN3B was set to GREEN
Added comment: PMID: 33811806
- 9 affected patients, all de novo (2 PTCs, 2 missense, multigenic CNVs)
- syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant ASD, congenital malformations, corpus callosum defects, and impaired growth.
- CNVs encompassing the gene have been found
Sources: Literature
Mendeliome v0.7464 DPYSL5 Michelle Torres gene: DPYSL5 was added
gene: DPYSL5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DPYSL5 were set to 33894126
Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Review for gene: DPYSL5 was set to GREEN
Added comment: Nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. The recurrent de novo p.Glu41Lys was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Both impaired DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development
Sources: Literature
Mendeliome v0.7464 VPS41 Kristin Rigbye reviewed gene: VPS41: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33764426; Phenotypes: Progressive neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7464 SCD Elena Savva gene: SCD was added
gene: SCD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCD were set to PMID: 33690217; 10899171
Phenotypes for gene: SCD were set to Adrenoleukodystrophy
Review for gene: SCD was set to RED
Added comment: PMID: 33690217 zebrafish K/O mimics the motor phenotype of ALD zebrafish

PMID: 10899171 null mouse was deficient in hepatic cholesterol esters and triglycerides despite the presence of normal activities of acyl-CoA, very low levels of triglycerides
Sources: Literature
Mendeliome v0.7464 CDC40 Zornitza Stark Phenotypes for gene: CDC40 were changed from Pontocerebellar hypoplasia; microcephaly; seizures to Pontocerebellar hypoplasia, type 15, MIM# 619302; microcephaly; seizures
Mendeliome v0.7463 CDC40 Zornitza Stark edited their review of gene: CDC40: Changed phenotypes: Pontocerebellar hypoplasia, type 15, MIM# 619302, microcephaly, seizures
Mendeliome v0.7463 PPIL1 Zornitza Stark Phenotypes for gene: PPIL1 were changed from Pontocerebellar hypoplasia; microcephaly; seizures to Pontocerebellar hypoplasia, type 14, MIM# 619301; microcephaly; seizures
Mendeliome v0.7462 PPIL1 Zornitza Stark edited their review of gene: PPIL1: Changed phenotypes: Pontocerebellar hypoplasia, type 14, MIM# 619301, microcephaly, seizures
Mendeliome v0.7462 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Mendeliome v0.7462 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291
Mendeliome v0.7461 BICD2 Zornitza Stark Publications for gene: BICD2 were set to
Mendeliome v0.7460 BICD2 Zornitza Stark Mode of inheritance for gene: BICD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7459 BICD2 Zornitza Stark reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23664116, 23664119, 23664120, 27751653, 28635954, 30054298, 29528393; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290, MONDO:0014121, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7459 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome, MIM#619293
Mendeliome v0.7458 VPS16 Zornitza Stark Phenotypes for gene: VPS16 were changed from Dystonia to Dystonia 30, MIM#619291
Mendeliome v0.7457 VPS16 Zornitza Stark edited their review of gene: VPS16: Changed phenotypes: Dystonia 30, MIM#619291
Mendeliome v0.7457 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Green List (High Evidence).
Mendeliome v0.7457 KCNQ5 Zornitza Stark Phenotypes for gene: KCNQ5 were changed from to Mental retardation, autosomal dominant 46, MIM# 617601
Mendeliome v0.7456 KCNQ5 Zornitza Stark Publications for gene: KCNQ5 were set to
Mendeliome v0.7455 KCNQ5 Zornitza Stark Mode of inheritance for gene: KCNQ5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7454 KCNQ5 Zornitza Stark reviewed gene: KCNQ5: Rating: GREEN; Mode of pathogenicity: None; Publications: 28669405, 30359776; Phenotypes: Mental retardation, autosomal dominant 46, MIM# 617601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7454 KCNK9 Zornitza Stark Gene: kcnk9 has been classified as Green List (High Evidence).
Mendeliome v0.7454 KCNK9 Zornitza Stark Phenotypes for gene: KCNK9 were changed from to Birk-Barel syndrome, MIM# 612292; MONDO:0012856
Mendeliome v0.7453 KCNK9 Zornitza Stark Publications for gene: KCNK9 were set to
Mendeliome v0.7452 KCNK9 Zornitza Stark Mode of inheritance for gene: KCNK9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.7451 KCNK9 Zornitza Stark reviewed gene: KCNK9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28333430, 27151206, 24980697, 18678320; Phenotypes: Birk-Barel syndrome, MIM# 612292, MONDO:0012856; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.7451 KCNK9 Ain Roesley reviewed gene: KCNK9: Rating: GREEN; Mode of pathogenicity: None; Publications: 18678320, 27151206; Phenotypes: Birk-Barel syndrome (MIM#612292); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Mendeliome v0.7451 ATL1 Zornitza Stark edited their review of gene: ATL1: Changed phenotypes: Neuropathy, hereditary sensory, type ID , MIM#613708, MONDO:0013381, Spastic paraplegia 3A, MIM 182600, Hereditary spastic paraplegia, AR
Mendeliome v0.7451 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Mendeliome v0.7451 ATL1 Zornitza Stark Gene: atl1 has been classified as Green List (High Evidence).
Mendeliome v0.7451 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381 to Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR
Mendeliome v0.7450 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from to Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381
Mendeliome v0.7449 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Mendeliome v0.7448 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7447 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21194679, 24604904, 22340599, 16401858, 16537571, 17657515, 28396731, 24473461, 26888483; Phenotypes: Neuropathy, hereditary sensory, type ID , MIM#613708, MONDO:0013381; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7447 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Mendeliome v0.7447 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1, MIM# 607426; MONDO:0011829
Mendeliome v0.7446 COQ2 Zornitza Stark Publications for gene: COQ2 were set to
Mendeliome v0.7445 COQ2 Zornitza Stark Mode of inheritance for gene: COQ2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7444 COQ2 Zornitza Stark reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16400613, 17332895, 17855635; Phenotypes: Coenzyme Q10 deficiency, primary, 1, MIM# 607426, MONDO:0011829; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7444 COA6 Zornitza Stark Gene: coa6 has been classified as Green List (High Evidence).
Mendeliome v0.7444 COA6 Zornitza Stark Phenotypes for gene: COA6 were changed from to Mitochondrial complex IV deficiency, nuclear type 13, MIM# 616501; Cardioencephalomyopathy, fatal infantile, MONDO:0014668
Mendeliome v0.7443 COA6 Zornitza Stark Publications for gene: COA6 were set to
Mendeliome v0.7442 COA6 Zornitza Stark Mode of inheritance for gene: COA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7441 COA6 Zornitza Stark reviewed gene: COA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24549041, 25339201, 31851937, 26160915; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 13, MIM# 616501, Cardioencephalomyopathy, fatal infantile, MONDO:0014668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7441 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Mendeliome v0.7441 CARS2 Zornitza Stark Phenotypes for gene: CARS2 were changed from to Combined oxidative phosphorylation deficiency 27, MIM# 616672; MONDO:0014728
Mendeliome v0.7440 CARS2 Zornitza Stark Publications for gene: CARS2 were set to
Mendeliome v0.7439 CARS2 Zornitza Stark Mode of inheritance for gene: CARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7438 CARS2 Zornitza Stark reviewed gene: CARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25361775, 25787132, 30139652; Phenotypes: Combined oxidative phosphorylation deficiency 27, MIM# 616672, MONDO:0014728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7438 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7438 PPP2R5C Sue White Classified gene: PPP2R5C as Amber List (moderate evidence)
Mendeliome v0.7438 PPP2R5C Sue White Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7437 PPP2R5C Sue White gene: PPP2R5C was added
gene: PPP2R5C was added to Mendeliome. Sources: Research
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5C were set to macrocephaly; intellectual disability
Penetrance for gene: PPP2R5C were set to Complete
Review for gene: PPP2R5C was set to AMBER
Added comment: Emerging unpublished evidence of monoallelic missense variants causing intellectual disability and macrocephaly
Sources: Research
Mendeliome v0.7436 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Mendeliome v0.7436 SLX4 Zornitza Stark Phenotypes for gene: SLX4 were changed from to Fanconi anaemia, complementation group P, MIM# 613951; MONDO:0013499
Mendeliome v0.7435 SLX4 Zornitza Stark Publications for gene: SLX4 were set to
Mendeliome v0.7434 SLX4 Zornitza Stark Mode of inheritance for gene: SLX4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7433 SLX4 Zornitza Stark reviewed gene: SLX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21240275, 21240277; Phenotypes: Fanconi anaemia, complementation group P, MIM# 613951, MONDO:0013499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7433 NLRP2 Zornitza Stark Publications for gene: NLRP2 were set to 30877238
Mendeliome v0.7432 NLRP2 Sarah Leigh reviewed gene: NLRP2: Rating: ; Mode of pathogenicity: None; Publications: 19300480, 29574422, 33090377; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.7432 SGCE Zornitza Stark Gene: sgce has been classified as Green List (High Evidence).
Mendeliome v0.7432 SGCE Zornitza Stark Phenotypes for gene: SGCE were changed from to Dystonia-11, myoclonic, MIM# 159900; MONDO:0008044
Mendeliome v0.7431 SGCE Zornitza Stark Publications for gene: SGCE were set to
Mendeliome v0.7430 SGCE Zornitza Stark Mode of inheritance for gene: SGCE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.7429 SGCE Zornitza Stark reviewed gene: SGCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528394, 12821748, 16227522; Phenotypes: Dystonia-11, myoclonic, MIM# 159900, MONDO:0008044; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.7429 PRKRA Zornitza Stark Gene: prkra has been classified as Green List (High Evidence).
Mendeliome v0.7429 PRKRA Zornitza Stark Phenotypes for gene: PRKRA were changed from to Dystonia 16, MIM# 612067; MONDO:0012789
Mendeliome v0.7428 PRKRA Zornitza Stark Publications for gene: PRKRA were set to
Mendeliome v0.7427 PRKRA Zornitza Stark Mode of inheritance for gene: PRKRA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7426 PRKRA Zornitza Stark reviewed gene: PRKRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 18243799, 25142429, 29279192; Phenotypes: Dystonia 16, MIM# 612067, MONDO:0012789; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7426 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Mendeliome v0.7426 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Mendeliome v0.7426 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from to Dystonia 28, childhood-onset 617284; MONDO:0015004
Mendeliome v0.7425 KMT2B Zornitza Stark Publications for gene: KMT2B were set to
Mendeliome v0.7424 KMT2B Zornitza Stark Mode of inheritance for gene: KMT2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7423 KMT2B Zornitza Stark reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 27839873, 27992417; Phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7423 CIZ1 Zornitza Stark Gene: ciz1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7423 CIZ1 Zornitza Stark Phenotypes for gene: CIZ1 were changed from to Dystonia 23 MIM#614860
Mendeliome v0.7422 CIZ1 Zornitza Stark Publications for gene: CIZ1 were set to
Mendeliome v0.7421 CIZ1 Zornitza Stark Mode of inheritance for gene: CIZ1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7420 CIZ1 Zornitza Stark Classified gene: CIZ1 as Amber List (moderate evidence)
Mendeliome v0.7420 CIZ1 Zornitza Stark Gene: ciz1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7419 CIZ1 Zornitza Stark reviewed gene: CIZ1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27163549, 29154038, 22447717; Phenotypes: Dystonia 23 MIM#614860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7419 NPAS2 Zornitza Stark Gene: npas2 has been classified as Red List (Low Evidence).
Mendeliome v0.7419 NPAS2 Zornitza Stark Phenotypes for gene: NPAS2 were changed from to Non-obstructive azoospermia
Mendeliome v0.7418 NPAS2 Zornitza Stark Publications for gene: NPAS2 were set to
Mendeliome v0.7417 NPAS2 Zornitza Stark Mode of inheritance for gene: NPAS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7416 NPAS2 Zornitza Stark Classified gene: NPAS2 as Red List (low evidence)
Mendeliome v0.7416 NPAS2 Zornitza Stark Gene: npas2 has been classified as Red List (Low Evidence).
Mendeliome v0.7415 NPAS2 Alison Compton changed review comment from: The brothers with NOA from consanguineous Turkish family, homozygous NM_002518.3(NPAS2) c.1363C>G; p.(Pro455Ala) variant identified. Heterozygous in mother, and fertile brother and sister. Not present in 1000 Genomes, EVS or gnomAD. Predicted to be “benign” by Polyphen2, and "neutral" by both SIFT and Mutation taster. Not predicted to in a functional domain. Not listed as a disease-gene in OMIM, no other 'pathogenic' or 'likely pathogenic' variants listed in ClinVar. Paper did not include any functional work.; to: Three brothers with NOA from consanguineous Turkish family, homozygous NM_002518.3(NPAS2) c.1363C>G; p.(Pro455Ala) variant identified. Found to be heterozygous in mother, and fertile brother and sister. Not present in 1000 Genomes, EVS or gnomAD. Predicted to be “benign” by Polyphen2, and "neutral" by both SIFT and Mutation taster. Not predicted to be within a functional domain. Gene not listed as a disease-gene in OMIM, no other 'pathogenic' or 'likely pathogenic' variants listed in ClinVar. Publication did not include any functional work as support.
Mendeliome v0.7415 PNKD Zornitza Stark Gene: pnkd has been classified as Green List (High Evidence).
Mendeliome v0.7415 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; MONDO:0007326
Mendeliome v0.7414 PNKD Zornitza Stark Publications for gene: PNKD were set to
Mendeliome v0.7413 PNKD Zornitza Stark Mode of inheritance for gene: PNKD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7412 PNKD Zornitza Stark reviewed gene: PNKD: Rating: GREEN; Mode of pathogenicity: None; Publications: 15262732, 15496428, 15824259, 19124534, 21487022; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800, MONDO:0007326; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7412 NPAS2 Alison Compton reviewed gene: NPAS2: Rating: RED; Mode of pathogenicity: Other; Publications: 25956372; Phenotypes: Non-obstructive azoospermia; Mode of inheritance: Unknown
Mendeliome v0.7412 MECR Zornitza Stark Gene: mecr has been classified as Green List (High Evidence).
Mendeliome v0.7412 MECR Zornitza Stark Phenotypes for gene: MECR were changed from to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282; MONDO:0015003
Mendeliome v0.7411 MECR Zornitza Stark Publications for gene: MECR were set to
Mendeliome v0.7410 MECR Zornitza Stark Mode of inheritance for gene: MECR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7409 MECR Zornitza Stark reviewed gene: MECR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27817865, 33401012, 31137067, 31070877; Phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, MIM# 617282, MONDO:0015003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7409 HPCA Zornitza Stark Gene: hpca has been classified as Green List (High Evidence).
Mendeliome v0.7409 HPCA Zornitza Stark Phenotypes for gene: HPCA were changed from to Dystonia 2, torsion, autosomal recessive, MIM# 224500; MONDO:0009141
Mendeliome v0.7408 HPCA Zornitza Stark Publications for gene: HPCA were set to
Mendeliome v0.7407 HPCA Zornitza Stark Mode of inheritance for gene: HPCA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7406 HPCA Zornitza Stark reviewed gene: HPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25799108, 30991467, 30145809; Phenotypes: Dystonia 2, torsion, autosomal recessive, MIM# 224500, MONDO:0009141; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7406 GNAL Zornitza Stark Gene: gnal has been classified as Green List (High Evidence).
Mendeliome v0.7406 GNAL Zornitza Stark Phenotypes for gene: GNAL were changed from to Dystonia 25, MIM# 615073; MONDO:0014033
Mendeliome v0.7405 GNAL Zornitza Stark Publications for gene: GNAL were set to
Mendeliome v0.7404 GNAL Zornitza Stark Mode of inheritance for gene: GNAL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7403 GNAL Zornitza Stark reviewed gene: GNAL: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222958, 33175450, 32180288; Phenotypes: Dystonia 25, MIM# 615073, MONDO:0014033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7403 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Mendeliome v0.7403 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707
Mendeliome v0.7402 ADCY5 Zornitza Stark Publications for gene: ADCY5 were set to
Mendeliome v0.7401 ADCY5 Zornitza Stark Mode of inheritance for gene: ADCY5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7400 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22782511, 24700542, 33051786, 32647899, 33704598; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7400 XPNPEP3 Zornitza Stark Classified gene: XPNPEP3 as Green List (high evidence)
Mendeliome v0.7400 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Mendeliome v0.7399 XPNPEP3 Zornitza Stark edited their review of gene: XPNPEP3: Added comment: PMID 20179356: two families with 5 individuals reported. Functional data, including animal models, supportive evidence for involvement in ciliary function.

PMID 32660933: Additional case reported.; Changed rating: GREEN; Changed publications: 20179356, 32660933
Mendeliome v0.7399 THAP1 Zornitza Stark Marked gene: THAP1 as ready
Mendeliome v0.7399 THAP1 Zornitza Stark Gene: thap1 has been classified as Green List (High Evidence).
Mendeliome v0.7399 THAP1 Zornitza Stark Phenotypes for gene: THAP1 were changed from to Dystonia 6, torsion, 602629; MONDO:0011264
Mendeliome v0.7398 THAP1 Zornitza Stark Publications for gene: THAP1 were set to
Mendeliome v0.7397 THAP1 Zornitza Stark Mode of inheritance for gene: THAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7396 THAP1 Zornitza Stark reviewed gene: THAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21793105, 22377579; Phenotypes: Dystonia 6, torsion, 602629, MONDO:0011264; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7396 EIF4G1 Bryony Thompson Tag for review was removed from gene: EIF4G1.
Mendeliome v0.7396 EIF4G1 Bryony Thompson Publications for gene: EIF4G1 were set to 21907011; 23408866; 25368108
Mendeliome v0.7395 CHST11 Zornitza Stark Marked gene: CHST11 as ready
Mendeliome v0.7395 CHST11 Zornitza Stark Gene: chst11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7395 CHST11 Zornitza Stark Classified gene: CHST11 as Amber List (moderate evidence)
Mendeliome v0.7395 CHST11 Zornitza Stark Gene: chst11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7394 CHST11 Zornitza Stark Tag SV/CNV tag was added to gene: CHST11.
Mendeliome v0.7394 CHST11 Zornitza Stark gene: CHST11 was added
gene: CHST11 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CHST11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST11 were set to 26436107; 29514872
Phenotypes for gene: CHST11 were set to Osteochondrodysplasia, brachydactyly, and overlapping malformed digits, MIM# 618167
Review for gene: CHST11 was set to AMBER
Added comment: Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) is characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum.

Two unrelated families reported, note one had a homozygous deletion. One family had 10 affected individuals.
Sources: Expert Review
Mendeliome v0.7393 SPRTN Zornitza Stark Phenotypes for gene: SPRTN were changed from Ruijs-Aalfs syndrome, MIM# 616200 to Ruijs-Aalfs syndrome, MIM# 616200; MONDO:0014527
Mendeliome v0.7392 SPRTN Zornitza Stark edited their review of gene: SPRTN: Changed phenotypes: Ruijs-Aalfs syndrome, MIM# 616200, MONDO:0014527
Mendeliome v0.7392 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Green List (High Evidence).
Mendeliome v0.7392 PSMB8 Zornitza Stark Phenotypes for gene: PSMB8 were changed from to Proteasome-associated autoinflammatory syndrome 1, MIM# 256040; MONDO:0054698
Mendeliome v0.7391 PSMB8 Zornitza Stark Publications for gene: PSMB8 were set to
Mendeliome v0.7390 PSMB8 Zornitza Stark Mode of inheritance for gene: PSMB8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7389 PSMB8 Zornitza Stark reviewed gene: PSMB8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129723, 21881205, 21852578, 21953331; Phenotypes: Proteasome-associated autoinflammatory syndrome 1, MIM# 256040, MONDO:0054698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7389 EFEMP1 Zornitza Stark Publications for gene: EFEMP1 were set to 32006683; 31792352
Mendeliome v0.7388 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Added comment: PMID 33807164: third unrelated family reported with CTD phenotype, single affected individual with bi-alllelic LoF variant, cutis laxa and multiple herniations.; Changed publications: 32006683, 31792352, 33807164
Mendeliome v0.7388 PPARG Zornitza Stark Gene: pparg has been classified as Green List (High Evidence).
Mendeliome v0.7388 PPARG Zornitza Stark Phenotypes for gene: PPARG were changed from to Lipodystrophy, familial partial, type 3, MIM# 604367; MONDO:0011448
Mendeliome v0.7387 PPARG Zornitza Stark Publications for gene: PPARG were set to
Mendeliome v0.7386 PPARG Zornitza Stark Mode of inheritance for gene: PPARG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7385 PPARG Zornitza Stark reviewed gene: PPARG: Rating: GREEN; Mode of pathogenicity: None; Publications: 10622252, 12453919, 11788685, 31863320; Phenotypes: Lipodystrophy, familial partial, type 3, MIM# 604367, MONDO:0011448; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7385 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Mendeliome v0.7385 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157
Mendeliome v0.7384 POLD1 Zornitza Stark Publications for gene: POLD1 were set to
Mendeliome v0.7383 POLD1 Zornitza Stark Mode of inheritance for gene: POLD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7382 POLD1 Zornitza Stark reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23770608, 33618333, 33369179, 32826474, 30023403, 29199204, 28791128; Phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7382 PLIN1 Zornitza Stark Tag disputed tag was added to gene: PLIN1.
Mendeliome v0.7382 PLIN1 Zornitza Stark Gene: plin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7382 PLIN1 Zornitza Stark Phenotypes for gene: PLIN1 were changed from to Lipodystrophy, familial partial, type 4, MIM# 613877
Mendeliome v0.7381 PLIN1 Zornitza Stark Publications for gene: PLIN1 were set to
Mendeliome v0.7380 PLIN1 Zornitza Stark Mode of inheritance for gene: PLIN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7379 PLIN1 Zornitza Stark Classified gene: PLIN1 as Amber List (moderate evidence)
Mendeliome v0.7379 PLIN1 Zornitza Stark Gene: plin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7378 PLIN1 Zornitza Stark reviewed gene: PLIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21345103, 31504636, 30020498, 25114292; Phenotypes: Lipodystrophy, familial partial, type 4, MIM# 613877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7378 PCYT1A Zornitza Stark Marked gene: PCYT1A as ready
Mendeliome v0.7378 PCYT1A Zornitza Stark Gene: pcyt1a has been classified as Green List (High Evidence).
Mendeliome v0.7378 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from to Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Congenital lipodystrophy
Mendeliome v0.7377 PCYT1A Zornitza Stark Publications for gene: PCYT1A were set to
Mendeliome v0.7376 PCYT1A Zornitza Stark Mode of inheritance for gene: PCYT1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7375 PCYT1A Zornitza Stark reviewed gene: PCYT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24387990, 24387991, 24889630; Phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940, Congenital lipodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7375 KCNJ6 Zornitza Stark Publications for gene: KCNJ6 were set to 25620207
Mendeliome v0.7374 KCNJ6 Zornitza Stark changed review comment from: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Three unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model.; to: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.
Mendeliome v0.7374 KCNJ6 Zornitza Stark edited their review of gene: KCNJ6: Changed publications: 25620207, 29852244
Mendeliome v0.7374 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Green List (High Evidence).
Mendeliome v0.7374 KCNJ6 Zornitza Stark Phenotypes for gene: KCNJ6 were changed from to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572
Mendeliome v0.7373 KCNJ6 Zornitza Stark Publications for gene: KCNJ6 were set to
Mendeliome v0.7372 KCNJ6 Zornitza Stark Mode of inheritance for gene: KCNJ6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7371 KCNJ6 Zornitza Stark reviewed gene: KCNJ6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25620207; Phenotypes: Keppen-Lubinsky syndrome, MIM# 614098, MONDO:0013572; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7371 EIF4G1 Zornitza Stark Gene: eif4g1 has been classified as Red List (Low Evidence).
Mendeliome v0.7371 EIF4G1 Zornitza Stark Phenotypes for gene: EIF4G1 were changed from to {Parkinson disease 18} 614251
Mendeliome v0.7370 EIF4G1 Zornitza Stark Tag disputed tag was added to gene: EIF4G1.
Mendeliome v0.7370 EIF4G1 Zornitza Stark Publications for gene: EIF4G1 were set to
Mendeliome v0.7369 EIF4G1 Zornitza Stark Mode of inheritance for gene: EIF4G1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7368 EIF4G1 Zornitza Stark Classified gene: EIF4G1 as Red List (low evidence)
Mendeliome v0.7368 EIF4G1 Zornitza Stark Gene: eif4g1 has been classified as Red List (Low Evidence).
Mendeliome v0.7367 EIF4G1 Zornitza Stark reviewed gene: EIF4G1: Rating: RED; Mode of pathogenicity: None; Publications: 21907011, 23408866, 25368108; Phenotypes: {Parkinson disease 18} 614251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7367 EIF4G1 Bryony Thompson Tag for review tag was added to gene: EIF4G1.
Mendeliome v0.7367 CIDEC Zornitza Stark Gene: cidec has been classified as Red List (Low Evidence).
Mendeliome v0.7367 CIDEC Zornitza Stark Phenotypes for gene: CIDEC were changed from to Lipodystrophy, familial partial, type 5, MIM# 615238
Mendeliome v0.7366 CIDEC Zornitza Stark Publications for gene: CIDEC were set to
Mendeliome v0.7365 CIDEC Zornitza Stark Mode of inheritance for gene: CIDEC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7364 CIDEC Zornitza Stark Classified gene: CIDEC as Red List (low evidence)
Mendeliome v0.7364 CIDEC Zornitza Stark Gene: cidec has been classified as Red List (Low Evidence).
Mendeliome v0.7363 CIDEC Zornitza Stark reviewed gene: CIDEC: Rating: RED; Mode of pathogenicity: None; Publications: 20049731; Phenotypes: Lipodystrophy, familial partial, type 5, MIM# 615238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7363 SAG Teresa Zhao Deleted their review
Mendeliome v0.7363 SAG Teresa Zhao reviewed gene: SAG: Rating: GREEN; Mode of pathogenicity: None; Publications: 22419846, 9452120; Phenotypes: Oguchi disease-1 (MIM#258100), AR, Retinitis pigmentosa 47 (MIM#613758); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7363 LIG3 Zornitza Stark changed review comment from: Three unrelated families and functional data.
Sources: Literature; to: Seven individuals from three unrelated families and functional data, variable ages of onset from early childhood to late adolescence.
Sources: Literature
Mendeliome v0.7363 LIG3 Zornitza Stark Gene: lig3 has been classified as Green List (High Evidence).
Mendeliome v0.7363 LIG3 Zornitza Stark Classified gene: LIG3 as Green List (high evidence)
Mendeliome v0.7363 LIG3 Zornitza Stark Gene: lig3 has been classified as Green List (High Evidence).
Mendeliome v0.7362 LIG3 Zornitza Stark gene: LIG3 was added
gene: LIG3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LIG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIG3 were set to 33855352
Phenotypes for gene: LIG3 were set to gut dysmotility; spasticity; ataxia; repetitive behaviours; neurogenic bladder; macular degeneration; leukoencephalopathy; cerebellar atrophy
Review for gene: LIG3 was set to GREEN
Added comment: Three unrelated families and functional data.
Sources: Literature
Mendeliome v0.7361 HNRNPDL Bryony Thompson Gene: hnrnpdl has been classified as Green List (High Evidence).
Mendeliome v0.7361 HNRNPDL Bryony Thompson Classified gene: HNRNPDL as Green List (high evidence)
Mendeliome v0.7361 HNRNPDL Bryony Thompson Gene: hnrnpdl has been classified as Green List (High Evidence).
Mendeliome v0.7360 HNRNPDL Bryony Thompson gene: HNRNPDL was added
gene: HNRNPDL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HNRNPDL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPDL were set to 24647604; 31267206; 31995753; 32407983; 32904822; 32367994
Phenotypes for gene: HNRNPDL were set to Muscular dystrophy, limb-girdle, autosomal dominant 3 MIM#609115
Review for gene: HNRNPDL was set to GREEN
gene: HNRNPDL was marked as current diagnostic
Added comment: At least 5 families reported with either D378H/N, and supporting functional assays demonstrating that these variants affect protein function. No other pathogenic variants have been reported. A VUS has been reported (along with another SETX variant) in an individual with a multi-system disorder, including a metabolic myopathy.
Sources: Expert list
Mendeliome v0.7359 JMJD1C Zornitza Stark Gene: jmjd1c has been classified as Green List (High Evidence).
Mendeliome v0.7359 JMJD1C Zornitza Stark Classified gene: JMJD1C as Green List (high evidence)
Mendeliome v0.7359 JMJD1C Zornitza Stark Gene: jmjd1c has been classified as Green List (High Evidence).
Mendeliome v0.7358 JMJD1C Zornitza Stark gene: JMJD1C was added
gene: JMJD1C was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JMJD1C were set to 26181491; 32996679
Phenotypes for gene: JMJD1C were set to Intellectual disability
Review for gene: JMJD1C was set to GREEN
Added comment: Reported in ID cohort (with Rett-like phenotypic overlap) with supporting functional studies (PMID: 26181491). 7 individuals with rare variants identified, and variants demonstrated to be de novo in 2, one with a Rett-like phenotype and the other with ID. Functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. JMJD1C protein shown to be widely expressed in brain regions and that its depletion compromised dendritic activity.

Splice-disrupting JMJD1C variant reported in association with learning disability and myoclonic epilepsy (PMID 32996679).

Disruption of gene due to balanced translocation (PMID 33591602) implicated in autism spectrum disease phenotype.
Sources: Expert Review
Mendeliome v0.7357 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Mendeliome v0.7357 CAVIN1 Zornitza Stark Phenotypes for gene: CAVIN1 were changed from to Lipodystrophy, congenital generalized, type 4, MIM# 613327; MONDO:0013225
Mendeliome v0.7356 CAVIN1 Zornitza Stark Publications for gene: CAVIN1 were set to
Mendeliome v0.7355 CAVIN1 Zornitza Stark Mode of inheritance for gene: CAVIN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7354 CAVIN1 Zornitza Stark reviewed gene: CAVIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19726876, 20300641, 20684003, 18840361; Phenotypes: Lipodystrophy, congenital generalized, type 4, MIM# 613327, MONDO:0013225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7354 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
Mendeliome v0.7354 CAV1 Zornitza Stark Phenotypes for gene: CAV1 were changed from to Lipodystrophy, familial partial, type 7, autosomal dominant MIM# 606721; Lipodystrophy, congenital generalized, type 3, autosomal recessive, MIM# 612526
Mendeliome v0.7353 CAV1 Zornitza Stark Publications for gene: CAV1 were set to
Mendeliome v0.7352 CAV1 Zornitza Stark Mode of inheritance for gene: CAV1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7351 CAV1 Zornitza Stark reviewed gene: CAV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18237401, 25898808, 11739396, 18211975, 27717241, 26176221, 33836561, 33776068, 32502478, 22474227, 28768485; Phenotypes: Lipodystrophy, familial partial, type 7, autosomal dominant MIM# 606721, Lipodystrophy, congenital generalized, type 3, autosomal recessive, MIM# 612526; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7351 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Mendeliome v0.7351 AFF4 Zornitza Stark Phenotypes for gene: AFF4 were changed from to CHOPS syndrome, MIM#616368; MONDO:0014609
Mendeliome v0.7350 AFF4 Zornitza Stark Publications for gene: AFF4 were set to
Mendeliome v0.7349 AFF4 Zornitza Stark Mode of inheritance for gene: AFF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7348 AFF4 Zornitza Stark reviewed gene: AFF4: Rating: GREEN; Mode of pathogenicity: Other; Publications: 25730767, 33248856, 31630891, 31058441; Phenotypes: CHOPS syndrome, MIM#616368, MONDO:0014609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7348 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Green List (high evidence)
Mendeliome v0.7348 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Green List (High Evidence).
Mendeliome v0.7347 DNAJB13 Zornitza Stark changed review comment from: Additional individual identified by VCGS laboratory, homozygous LoF variant.; to: Additional individual identified by VCGS laboratory, homozygous LoF variant and PCD.
Mendeliome v0.7347 DNAJB13 Zornitza Stark changed review comment from: Additional individual identified by VCGS laboratory.; to: Additional individual identified by VCGS laboratory, homozygous LoF variant.
Mendeliome v0.7347 DNAJB13 Zornitza Stark edited their review of gene: DNAJB13: Added comment: Additional individual identified by VCGS laboratory.; Changed rating: GREEN
Mendeliome v0.7347 GCGR Zornitza Stark Gene: gcgr has been classified as Green List (High Evidence).
Mendeliome v0.7347 GCGR Zornitza Stark Classified gene: GCGR as Green List (high evidence)
Mendeliome v0.7347 GCGR Zornitza Stark Gene: gcgr has been classified as Green List (High Evidence).
Mendeliome v0.7346 GCGR Zornitza Stark gene: GCGR was added
gene: GCGR was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GCGR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCGR were set to 19657311; 25695890; 27933176; 30032256; 30294546
Phenotypes for gene: GCGR were set to Mahvash disease, MIM# 619290
Review for gene: GCGR was set to GREEN
Added comment: Mahvash disease (MVAH) is caused by inactivating mutations in the glucagon receptor, leading to alpha-cell hyperplasia of the pancreas, hyperglucagonaemia without glucagonoma syndrome, and occasional hypoglycaemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumours.

More than 5 unrelated families reported.
Sources: Expert list
Mendeliome v0.7345 VPS4A Zornitza Stark Phenotypes for gene: VPS4A were changed from Neurodevelopmental disorder to CIMDAG syndrome MIM# 619273
Mendeliome v0.7344 VPS4A Zornitza Stark reviewed gene: VPS4A: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: CIMDAG syndrome MIM# 619273; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7344 MED27 Zornitza Stark Phenotypes for gene: MED27 were changed from Intellectual disability; cerebellar hypoplasia; dystonia to Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286
Mendeliome v0.7343 MED27 Zornitza Stark reviewed gene: MED27: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7343 ABCB6 Zornitza Stark Gene: abcb6 has been classified as Green List (High Evidence).
Mendeliome v0.7343 ABCB6 Zornitza Stark Phenotypes for gene: ABCB6 were changed from to Pseudohyperkalemia, familial, 2, due to red cell leak, MIM# 609153; Microphthalmia, isolated, with coloboma 7, MIM# 614497; Dyschromatosis universalis hereditaria 3, MIM# 615402
Mendeliome v0.7342 ABCB6 Zornitza Stark Publications for gene: ABCB6 were set to
Mendeliome v0.7341 ABCB6 Zornitza Stark Mode of inheritance for gene: ABCB6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7340 ABCB6 Zornitza Stark reviewed gene: ABCB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23180570; Phenotypes: Pseudohyperkalemia, familial, 2, due to red cell leak, MIM# 609153, Microphthalmia, isolated, with coloboma 7, MIM# 614497, Dyschromatosis universalis hereditaria 3, MIM# 615402; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7340 ABCA1 Zornitza Stark Gene: abca1 has been classified as Green List (High Evidence).
Mendeliome v0.7340 PRDM15 Zornitza Stark Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7340 PRDM15 Zornitza Stark Classified gene: PRDM15 as Amber List (moderate evidence)
Mendeliome v0.7340 PRDM15 Zornitza Stark Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7339 PRDM15 Zornitza Stark gene: PRDM15 was added
gene: PRDM15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080
Phenotypes for gene: PRDM15 were set to Steroid resistant nephrotic syndrome; Holoprosencephaly
Review for gene: PRDM15 was set to AMBER
Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic SRNS including HPE, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data focused on the brain phenotype. Two additional homozygous missense identified with isolated SRNS.
Sources: Literature
Mendeliome v0.7338 ZIC2 Zornitza Stark Gene: zic2 has been classified as Green List (High Evidence).
Mendeliome v0.7338 ZIC2 Zornitza Stark Phenotypes for gene: ZIC2 were changed from to Holoprosencephaly 5, MIM# 609637; MONDO:0012322
Mendeliome v0.7337 ZIC2 Zornitza Stark Publications for gene: ZIC2 were set to
Mendeliome v0.7336 ZIC2 Zornitza Stark Mode of inheritance for gene: ZIC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7335 ZIC2 Zornitza Stark reviewed gene: ZIC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771712, 11285244; Phenotypes: Holoprosencephaly 5, MIM# 609637, MONDO:0012322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7335 TGIF1 Zornitza Stark Marked gene: TGIF1 as ready
Mendeliome v0.7335 TGIF1 Zornitza Stark Gene: tgif1 has been classified as Green List (High Evidence).
Mendeliome v0.7335 TGIF1 Zornitza Stark Phenotypes for gene: TGIF1 were changed from to Holoprosencephaly 4, MIM# 142946; MONDO:0007734
Mendeliome v0.7334 TGIF1 Zornitza Stark Publications for gene: TGIF1 were set to
Mendeliome v0.7333 TGIF1 Zornitza Stark Mode of inheritance for gene: TGIF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7332 TGIF1 Zornitza Stark reviewed gene: TGIF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835638, 16323008; Phenotypes: Holoprosencephaly 4, MIM# 142946, MONDO:0007734; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7332 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Mendeliome v0.7332 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from to Holoprosencephaly 2, MIM# 157170; MONDO:0007999
Mendeliome v0.7331 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Mendeliome v0.7330 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7329 SIX3 Zornitza Stark reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10369266, 16323008, 19346217; Phenotypes: Holoprosencephaly 2, MIM# 157170, MONDO:0007999; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7329 DISP1 Zornitza Stark Gene: disp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7329 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from to Holoprosencephaly
Mendeliome v0.7328 DISP1 Zornitza Stark Publications for gene: DISP1 were set to
Mendeliome v0.7327 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7326 DISP1 Zornitza Stark Classified gene: DISP1 as Amber List (moderate evidence)
Mendeliome v0.7326 DISP1 Zornitza Stark Gene: disp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7325 DISP1 Zornitza Stark reviewed gene: DISP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19184110, 26748417, 23542665; Phenotypes: Holoprosencephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7325 TBX3 Zornitza Stark Marked gene: TBX3 as ready
Mendeliome v0.7325 TBX3 Zornitza Stark Gene: tbx3 has been classified as Green List (High Evidence).
Mendeliome v0.7325 TBX3 Zornitza Stark Phenotypes for gene: TBX3 were changed from to Ulnar-mammary syndrome, MIM# 181450; MONDO:0008411
Mendeliome v0.7324 TBX3 Zornitza Stark Publications for gene: TBX3 were set to
Mendeliome v0.7323 TBX3 Zornitza Stark Mode of inheritance for gene: TBX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7322 TBX3 Zornitza Stark reviewed gene: TBX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9207801, 19938096, 28145909; Phenotypes: Ulnar-mammary syndrome, MIM# 181450, MONDO:0008411; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7322 SALL1 Zornitza Stark Gene: sall1 has been classified as Green List (High Evidence).
Mendeliome v0.7322 SALL1 Zornitza Stark Phenotypes for gene: SALL1 were changed from to Townes-Brocks syndrome 1, MIM#107480; MONDO:0054581
Mendeliome v0.7321 SALL1 Zornitza Stark Mode of inheritance for gene: SALL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7320 SALL1 Zornitza Stark reviewed gene: SALL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Townes-Brocks syndrome 1, MIM#107480, MONDO:0054581; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7320 RPS17 Zornitza Stark Phenotypes for gene: RPS17 were changed from Diamond-Blackfan anemia 4, MIM# 612527 to Diamond-Blackfan anaemia 4, MIM# 612527; MONDO:0012924
Mendeliome v0.7319 RPL35A Zornitza Stark Phenotypes for gene: RPL35A were changed from Diamond-Blackfan anemia 5, MIM# 612528 to Diamond-Blackfan anemia 5, MIM# 612528; MONDO:0012925
Mendeliome v0.7318 RPL35A Zornitza Stark edited their review of gene: RPL35A: Changed phenotypes: Diamond-Blackfan anemia 5, MIM# 612528, MONDO:0012925
Mendeliome v0.7318 FANCD2 Zornitza Stark Phenotypes for gene: FANCD2 were changed from Fanconi anemia, complementation group D2, MIM#227646 to Fanconi anemia, complementation group D2, MIM#227646; MONDO:0009214
Mendeliome v0.7317 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
Mendeliome v0.7317 HELLS Zornitza Stark Phenotypes for gene: HELLS were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM# 616911; MONDO:0014829
Mendeliome v0.7316 HELLS Zornitza Stark Publications for gene: HELLS were set to
Mendeliome v0.7315 HELLS Zornitza Stark Mode of inheritance for gene: HELLS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7314 HELLS Zornitza Stark reviewed gene: HELLS: Rating: GREEN; Mode of pathogenicity: None; Publications: 26216346; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM# 616911, MONDO:0014829; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7314 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
Mendeliome v0.7314 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Mendeliome v0.7314 ZBTB24 Zornitza Stark Phenotypes for gene: ZBTB24 were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 2, MIM# 614069; MONDO:0013553
Mendeliome v0.7313 ZBTB24 Zornitza Stark Publications for gene: ZBTB24 were set to
Mendeliome v0.7312 ZBTB24 Zornitza Stark Mode of inheritance for gene: ZBTB24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7311 ZBTB24 Zornitza Stark reviewed gene: ZBTB24: Rating: GREEN; Mode of pathogenicity: None; Publications: 21596365, 21906047, 23486536; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 2, MIM# 614069, MONDO:0013553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7311 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
Mendeliome v0.7311 CDCA7 Zornitza Stark Phenotypes for gene: CDCA7 were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910; MONDO:0014828
Mendeliome v0.7310 CDCA7 Zornitza Stark Publications for gene: CDCA7 were set to
Mendeliome v0.7309 CDCA7 Zornitza Stark Mode of inheritance for gene: CDCA7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7308 CDCA7 Zornitza Stark reviewed gene: CDCA7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26216346; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910, MONDO:0014828; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7308 XRCC4 Zornitza Stark Phenotypes for gene: XRCC4 were changed from Short stature, microcephaly, and endocrine dysfunction (MIM#616541) to Short stature, microcephaly, and endocrine dysfunction, MIM# 616541; MONDO:0014686
Mendeliome v0.7307 XRCC4 Zornitza Stark reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Short stature, microcephaly, and endocrine dysfunction, MIM# 616541, MONDO:0014686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7307 XPC Zornitza Stark Gene: xpc has been classified as Green List (High Evidence).
Mendeliome v0.7307 XPC Zornitza Stark Phenotypes for gene: XPC were changed from to Xeroderma pigmentosum, group C, MIM# 278720; MONDO:0010211
Mendeliome v0.7306 XPC Zornitza Stark Publications for gene: XPC were set to
Mendeliome v0.7305 XPC Zornitza Stark Mode of inheritance for gene: XPC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7304 XPC Zornitza Stark reviewed gene: XPC: Rating: GREEN; Mode of pathogenicity: None; Publications: 10447254; Phenotypes: Xeroderma pigmentosum, group C, MIM# 278720, MONDO:0010211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7304 XPA Zornitza Stark Gene: xpa has been classified as Green List (High Evidence).
Mendeliome v0.7304 XPA Zornitza Stark Phenotypes for gene: XPA were changed from to Xeroderma pigmentosum, group A , MIM#278700; MONDO:0010210
Mendeliome v0.7303 XPA Zornitza Stark Publications for gene: XPA were set to
Mendeliome v0.7302 XPA Zornitza Stark Mode of inheritance for gene: XPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7301 XPA Zornitza Stark reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 2234061, 1372102; Phenotypes: Xeroderma pigmentosum, group A , MIM#278700, MONDO:0010210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7301 RMI2 Zornitza Stark Gene: rmi2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7301 RMI2 Zornitza Stark Phenotypes for gene: RMI2 were changed from to Bloom-like syndrome
Mendeliome v0.7300 RMI2 Zornitza Stark Publications for gene: RMI2 were set to
Mendeliome v0.7299 RMI2 Zornitza Stark Mode of inheritance for gene: RMI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7298 RMI2 Zornitza Stark Classified gene: RMI2 as Amber List (moderate evidence)
Mendeliome v0.7298 RMI2 Zornitza Stark Gene: rmi2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7297 RMI2 Zornitza Stark reviewed gene: RMI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27977684; Phenotypes: Bloom-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7297 RAD51 Zornitza Stark edited their review of gene: RAD51: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7297 RAD51 Zornitza Stark Gene: rad51 has been classified as Green List (High Evidence).
Mendeliome v0.7297 RAD51 Zornitza Stark Phenotypes for gene: RAD51 were changed from to Fanconi anaemia, complementation group R, MIM# 617244
Mendeliome v0.7296 RAD51 Zornitza Stark Publications for gene: RAD51 were set to
Mendeliome v0.7295 RAD51 Zornitza Stark Mode of inheritance for gene: RAD51 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7294 RAD51 Zornitza Stark reviewed gene: RAD51: Rating: GREEN; Mode of pathogenicity: None; Publications: 26253028, 26681308, 30907510; Phenotypes: Fanconi anaemia, complementation group R, MIM# 617244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7294 POLH Zornitza Stark Gene: polh has been classified as Green List (High Evidence).
Mendeliome v0.7294 POLH Zornitza Stark Phenotypes for gene: POLH were changed from to Xeroderma pigmentosum, variant type, MIM# 278750; MONDO:0010214
Mendeliome v0.7293 POLH Zornitza Stark Publications for gene: POLH were set to
Mendeliome v0.7292 POLH Zornitza Stark Mode of inheritance for gene: POLH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7291 POLH Zornitza Stark reviewed gene: POLH: Rating: GREEN; Mode of pathogenicity: None; Publications: 10385124, 10398605; Phenotypes: Xeroderma pigmentosum, variant type, MIM# 278750, MONDO:0010214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7291 NEUROD2 Zornitza Stark Phenotypes for gene: NEUROD2 were changed from Epileptic encephalopathy, early infantile, 72, MIM# 618374 to Epileptic encephalopathy, early infantile, 72, MIM# 618374; Intellectual disability
Mendeliome v0.7290 NEUROD2 Zornitza Stark Publications for gene: NEUROD2 were set to 30323019
Mendeliome v0.7289 NEUROD2 Zornitza Stark edited their review of gene: NEUROD2: Added comment: Additional two individuals reported with de novo variants and predominantly ID phenotype.; Changed publications: 33438828, 30323019; Changed phenotypes: Epileptic encephalopathy, early infantile, 72, MIM# 618374
Mendeliome v0.7289 MRE11 Zornitza Stark Gene: mre11 has been classified as Green List (High Evidence).
Mendeliome v0.7289 MRE11 Zornitza Stark Phenotypes for gene: MRE11 were changed from to Ataxia-telangiectasia-like disorder 1, MIM# 604391; MONDO:0024557
Mendeliome v0.7288 MRE11 Zornitza Stark Publications for gene: MRE11 were set to
Mendeliome v0.7287 MRE11 Zornitza Stark Mode of inheritance for gene: MRE11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7286 MRE11 Zornitza Stark reviewed gene: MRE11: Rating: GREEN; Mode of pathogenicity: None; Publications: 10612394, 11371508, 15269180, 22863007, 24332946, 21227757; Phenotypes: Ataxia-telangiectasia-like disorder 1, MIM# 604391, MONDO:0024557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7286 MPLKIP Zornitza Stark Gene: mplkip has been classified as Green List (High Evidence).
Mendeliome v0.7286 MPLKIP Zornitza Stark Phenotypes for gene: MPLKIP were changed from to Trichothiodystrophy 4, nonphotosensitive, MIM# 234050; MONDO:0021013
Mendeliome v0.7285 MPLKIP Zornitza Stark Publications for gene: MPLKIP were set to
Mendeliome v0.7284 MPLKIP Zornitza Stark Mode of inheritance for gene: MPLKIP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7283 MPLKIP Zornitza Stark reviewed gene: MPLKIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15645389, 16977596; Phenotypes: Trichothiodystrophy 4, nonphotosensitive, MIM# 234050, MONDO:0021013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7283 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
Mendeliome v0.7283 PIK3CD Zornitza Stark Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14B, autosomal recessive, MIM# 619281; Immunodeficiency 14A, autosomal dominant, MIM# 615513
Mendeliome v0.7282 PIK3CD Zornitza Stark Publications for gene: PIK3CD were set to
Mendeliome v0.7281 PIK3CD Zornitza Stark Mode of inheritance for gene: PIK3CD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7280 PIK3CD Zornitza Stark reviewed gene: PIK3CD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30040974, 30336224, 29180244, 16984281, 24136356, 24165795, 24610295; Phenotypes: Immunodeficiency 14B, autosomal recessive, MIM# 619281, Immunodeficiency 14A, autosomal dominant, MIM# 615513; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7280 GTF2H5 Zornitza Stark Marked gene: GTF2H5 as ready
Mendeliome v0.7280 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Mendeliome v0.7280 GTF2H5 Zornitza Stark Phenotypes for gene: GTF2H5 were changed from to Trichothiodystrophy 3, photosensitive, MIM# 616395; MONDO:0014619
Mendeliome v0.7279 GTF2H5 Zornitza Stark Publications for gene: GTF2H5 were set to
Mendeliome v0.7278 GTF2H5 Zornitza Stark Mode of inheritance for gene: GTF2H5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7277 GTF2H5 Zornitza Stark reviewed gene: GTF2H5: Rating: GREEN; Mode of pathogenicity: None; Publications: 15220921, 30359777, 24986372; Phenotypes: Trichothiodystrophy 3, photosensitive, MIM# 616395, MONDO:0014619; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7277 GTF2E2 Zornitza Stark Marked gene: GTF2E2 as ready
Mendeliome v0.7277 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7277 GTF2E2 Zornitza Stark Phenotypes for gene: GTF2E2 were changed from to Trichothiodystrophy 6, nonphotosensitive, MIM# 616943; MONDO:0014841
Mendeliome v0.7276 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to
Mendeliome v0.7275 GTF2E2 Zornitza Stark Mode of inheritance for gene: GTF2E2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7274 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Amber List (moderate evidence)
Mendeliome v0.7274 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7273 GTF2E2 Zornitza Stark reviewed gene: GTF2E2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26996949; Phenotypes: Trichothiodystrophy 6, nonphotosensitive, MIM# 616943, MONDO:0014841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7273 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Mendeliome v0.7273 FANCL Zornitza Stark Phenotypes for gene: FANCL were changed from to Fanconi anemia, complementation group L, MIM# 614083; MONDO:0013566
Mendeliome v0.7272 FANCL Zornitza Stark Publications for gene: FANCL were set to
Mendeliome v0.7271 FANCL Zornitza Stark Mode of inheritance for gene: FANCL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7270 FANCL Zornitza Stark reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19405097, 25754594, 33394227, 33224012; Phenotypes: Fanconi anemia, complementation group L, MIM# 614083, MONDO:0013566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7270 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Mendeliome v0.7270 FANCI Zornitza Stark Phenotypes for gene: FANCI were changed from to Fanconi anemia, complementation group I, MIM# 609053; MONDO:0012186
Mendeliome v0.7269 FANCI Zornitza Stark Publications for gene: FANCI were set to
Mendeliome v0.7268 FANCI Zornitza Stark Mode of inheritance for gene: FANCI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7267 FANCI Zornitza Stark reviewed gene: FANCI: Rating: GREEN; Mode of pathogenicity: None; Publications: 17452773; Phenotypes: Fanconi anemia, complementation group I, MIM# 609053, MONDO:0012186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7267 FANCG Zornitza Stark Gene: fancg has been classified as Green List (High Evidence).
Mendeliome v0.7267 FANCG Zornitza Stark Phenotypes for gene: FANCG were changed from to Fanconi anaemia, complementation group G, MIM# 614082; MONDO:0013565
Mendeliome v0.7266 FANCG Zornitza Stark Publications for gene: FANCG were set to
Mendeliome v0.7265 FANCG Zornitza Stark Mode of inheritance for gene: FANCG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7264 FANCG Zornitza Stark reviewed gene: FANCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 9806548, 12552564; Phenotypes: Fanconi anaemia, complementation group G, MIM# 614082, MONDO:0013565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7264 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Mendeliome v0.7264 FANCF Zornitza Stark Phenotypes for gene: FANCF were changed from to Fanconi anaemia, complementation group F 603467; MONDO:0011325
Mendeliome v0.7263 FANCF Zornitza Stark Publications for gene: FANCF were set to
Mendeliome v0.7262 FANCF Zornitza Stark Mode of inheritance for gene: FANCF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7261 FANCF Zornitza Stark reviewed gene: FANCF: Rating: GREEN; Mode of pathogenicity: None; Publications: 10615118, 31288759; Phenotypes: Fanconi anaemia, complementation group F 603467, MONDO:0011325; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7261 FANCE Zornitza Stark Gene: fance has been classified as Green List (High Evidence).
Mendeliome v0.7261 FANCE Zornitza Stark Phenotypes for gene: FANCE were changed from to Fanconi anaemia, complementation group E, MIM# 600901; MONDO:0010953
Mendeliome v0.7260 FANCE Zornitza Stark Publications for gene: FANCE were set to
Mendeliome v0.7259 FANCE Zornitza Stark Mode of inheritance for gene: FANCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7258 FANCE Zornitza Stark reviewed gene: FANCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11001585, 31586946, 7662964, 9382107, 9147877, 10205272; Phenotypes: Fanconi anaemia, complementation group E, MIM# 600901, MONDO:0010953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7258 MDM2 Zornitza Stark Gene: mdm2 has been classified as Red List (Low Evidence).
Mendeliome v0.7258 MDM2 Zornitza Stark Phenotypes for gene: MDM2 were changed from to Lessel-Kubisch syndrome, MIM# 618681
Mendeliome v0.7257 MDM2 Zornitza Stark Publications for gene: MDM2 were set to
Mendeliome v0.7256 MDM2 Zornitza Stark Mode of inheritance for gene: MDM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7255 MDM2 Zornitza Stark Classified gene: MDM2 as Red List (low evidence)
Mendeliome v0.7255 MDM2 Zornitza Stark Gene: mdm2 has been classified as Red List (Low Evidence).
Mendeliome v0.7254 MDM2 Chern Lim reviewed gene: MDM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28846075; Phenotypes: ?Lessel-Kubisch syndrome (MIM#618681); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7254 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021) to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721
Mendeliome v0.7253 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021) to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021)
Mendeliome v0.7252 NDUFB11 Zornitza Stark Gene: ndufb11 has been classified as Green List (High Evidence).
Mendeliome v0.7252 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021)
Mendeliome v0.7251 NDUFB11 Zornitza Stark Publications for gene: NDUFB11 were set to
Mendeliome v0.7250 NDUFB11 Zornitza Stark Mode of inheritance for gene: NDUFB11 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 v0.7249 NDUFB11 Kristin Rigbye changed review comment from: Variable syndromic features have been observed in affected individuals, however anaemia and cardiomyopathy appear to be consistent features in males and females, respectively (PMID: 28050600, PMID: 30423443, PMID: 27488349).

Affected females have previously been reported with inherited pathogenic variants from their unaffected mothers. It has been suggested that this may be due to patterns of somatic X-chromosome inactivation, mosaicism or additional genetic or external factors (PMID: 28050600).

Affected females have been reported with null alleles, whereas affected males have only been identified with missense variants or a recurrent single residue in-frame deletion, suggesting that some residual enzyme activity is required for males to be viable, whereas complete loss of function variants may be lethal when hemizygous (PMID: 30423443).
Note: female carriers of missense variants have not been reported as clinically affected.

Western blots from cells of male patients with the recurrent F93del variant showed reduced protein levels, and recombinant cells demonstrated a proliferation defect, consistent with the anaemia phenotype (PMID: 27488349).; to: Variable syndromic features have been observed in affected individuals, however anaemia and cardiomyopathy appear to be consistent features in males and females, respectively (PMID: 28050600, PMID: 30423443, PMID: 27488349).

It has been suggested that heterozygous females do not display the severe phenotype associated with mitochondrial complex 1 deficiency due to highly skewed XCI favouring expression of the wild type allele, whereas these null variants result in a severe lethal disorder in hemizygous males (PMID: 25772934).

Affected females have previously been reported with inherited pathogenic variants from their unaffected mothers. It has been suggested that this may be due to patterns of somatic X-chromosome inactivation, mosaicism or additional genetic or external factors (PMID: 28050600).

Affected females have been reported with null alleles, whereas affected males have only been identified with missense variants or a recurrent single residue in-frame deletion, suggesting that some residual enzyme activity is required for males to be viable, whereas complete loss of function variants may be lethal when hemizygous (PMID: 30423443).
Note: female carriers of missense variants have not been reported as clinically affected.

Western blots from cells of male patients with the recurrent F93del variant showed reduced protein levels, and recombinant cells demonstrated a proliferation defect, consistent with the anaemia phenotype (PMID: 27488349).
Mendeliome v0.7249 NDUFB11 Kristin Rigbye reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 28050600, 27488349, 30423443, 27488349; Phenotypes: Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952), Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); 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 v0.7249 FANCC Zornitza Stark Gene: fancc has been classified as Green List (High Evidence).