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Mendeliome v1.3353 FAP Sangavi Sivagnanasundram gene: FAP was added
gene: FAP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FAP were set to 40949908
Phenotypes for gene: FAP were set to congenital pulmonary airway malformation MONDO:0016580
Review for gene: FAP was set to RED
Added comment: Only 1 reported fetus with a diagnosis of congenital pulmonary airway malformation
Heterozygous variant identified - c.T269G:p.L90W.
The variant is present in gnomAD v4.1 - EAS AF - 0.007% (4 hets)
Sources: Literature
Mendeliome v1.2958 CCDC189 Zornitza Stark gene: CCDC189 was added
gene: CCDC189 was added to Mendeliome. Sources: Literature
new gene name tags were added to gene: CCDC189.
Mode of inheritance for gene: CCDC189 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC189 were set to 40759592
Phenotypes for gene: CCDC189 were set to Spermatogenic failure, MONDO:0004983, CCDC189-related
Review for gene: CCDC189 was set to RED
Added comment: Single individual with biallelic variants. Limited functional data.

New HGNC approved name CFAP119.
Sources: Literature
Mendeliome v1.2802 CFAP43 Zornitza Stark Classified gene: CFAP43 as Amber List (moderate evidence)
Mendeliome v1.2802 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2801 CFAP43 Zornitza Stark edited their review of gene: CFAP43: Added comment: DISPUTED by ClinGen for biallelic association with PCD.; Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2670 CFAP221 Zornitza Stark Phenotypes for gene: CFAP221 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 55, MIM# 279000
Mendeliome v1.2669 CFAP221 Zornitza Stark Publications for gene: CFAP221 were set to 31636325
Mendeliome v1.2668 CFAP221 Zornitza Stark Classified gene: CFAP221 as Green List (high evidence)
Mendeliome v1.2668 CFAP221 Zornitza Stark Gene: cfap221 has been classified as Green List (High Evidence).
Mendeliome v1.2667 CFAP221 Zornitza Stark edited their review of gene: CFAP221: Added comment: Five additional individuals reported, although two of them are homozygous for the same variant.; Changed rating: GREEN; Changed publications: 31636325, 39362668, 40250778, 38960684, 40272718; Changed phenotypes: Ciliary dyskinesia, primary, 55, MIM# 279000
Mendeliome v1.2417 CFAP221 Achchuthan Shanmugasundram reviewed gene: CFAP221: Rating: AMBER; Mode of pathogenicity: None; Publications: 31636325, 39362668; Phenotypes: primary ciliary dyskinesia, MONDO:0016575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2409 CFAP54 Zornitza Stark Phenotypes for gene: CFAP54 were changed from Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation to Ciliary dyskinesia, primary, 54, MIM:621125; Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation
Mendeliome v1.2408 CFAP54 Zornitza Stark Publications for gene: CFAP54 were set to 26224312; 36593121
Mendeliome v1.2407 CFAP54 Zornitza Stark Classified gene: CFAP54 as Green List (high evidence)
Mendeliome v1.2407 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Green List (High Evidence).
Mendeliome v1.2400 CFAP54 Achchuthan Shanmugasundram reviewed gene: CFAP54: Rating: GREEN; Mode of pathogenicity: None; Publications: 39362668; Phenotypes: Ciliary dyskinesia, primary, 54, OMIM:621125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2398 CFAP74 Achchuthan Shanmugasundram reviewed gene: CFAP74: Rating: GREEN; Mode of pathogenicity: None; Publications: 32555313, 36047773, 39362668; Phenotypes: Ciliary dyskinesia, primary, 49, without situs inversus, OMIM:620197; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2370 CFAP54 Zornitza Stark Classified gene: CFAP54 as Amber List (moderate evidence)
Mendeliome v1.2370 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2369 CFAP54 Zornitza Stark edited their review of gene: CFAP54: Added comment: PMID 37725231: three probands from two families with PCD, supportive mouse models x2.; Changed rating: AMBER; Changed publications: 26224312, 36593121, 37725231; Changed phenotypes: Spermatogenic failure 98, MIM# 621124, HCiliary dyskinesia, primary, 54, MIM# 621125
Mendeliome v1.2368 CFAP54 Zornitza Stark Marked gene: CFAP54 as ready
Mendeliome v1.2368 CFAP54 Zornitza Stark Gene: cfap54 has been classified as Red List (Low Evidence).
Mendeliome v1.2368 CFAP54 Zornitza Stark gene: CFAP54 was added
gene: CFAP54 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP54 were set to 26224312; 36593121
Phenotypes for gene: CFAP54 were set to Spermatogenic failure 98, MIM# 621124; Hydrocephalus, male infertility, mucus accumulation
Review for gene: CFAP54 was set to RED
Added comment: PMID 36593121: Three men identified with bi-allelic variants and multiple morphologic abnormalities of the flagella or non-obstructive azoospermia.

PMID: 26224312: Homozygous mice have PCD characterized by hydrocephalus, male infertility (spermatogenesis defects in flagella maturation), and mucus accumulation. Brain analysis showed mild dilatation of the lateral ventricles. Tracheal cilia beat frequency was significantly reduced. The gene was highest expressed in the testis and lungs
Sources: Literature
Mendeliome v1.2354 CFAP47 Zornitza Stark Phenotypes for gene: CFAP47 were changed from Spermatogenic failure, X-linked, 3, MIM# 301059; asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF) to Spermatogenic failure, X-linked, 3, MIM# 301059; Cystic kidney disease MONDO:0002473
Mendeliome v1.2353 CFAP47 Zornitza Stark Publications for gene: CFAP47 were set to PMID: 33472045
Mendeliome v1.2351 CFAP47 Chirag Patel changed review comment from: 3 individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.; to: 3 Japanese individuals with bilateral kidney cysts with mild enlargement of kidneys (mean age at Dx ~70yrs). They were all undergoing treatment for hypertension, had mean eGFR of ~31, None of them had any liver cysts, infertility, or any family history of cystic kidney disease. WGS after negative clinical diagnostic testing, identified 3 missense variants in CFAP47 gene [p.(Arg870Gln), p.(Phe516Cys), and p.(Gly6Asp)]. The variants were rare in gnomAD but had equivocal in silico prediction scores, and would be reported as VUS using ACMG criteria. Segregation was not possible as their mothers were deceased. CFAP47 encodes cilia and flagella associated protein 47 a protein that plays a role in the formation and function of cilia and flagella. It is is expressed in primary cilia of human kidney tubules. Knockout (KO) mice exhibited larger kidneys with vacuolation of tubular cells and tubular dilation, providing evidence that CFAP47 is a causative gene involved in cyst formation.
Mendeliome v1.2351 CFAP47 Chirag Patel reviewed gene: CFAP47: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 39698362; Phenotypes: Cystic kidney disease MONDO:0002473; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.1959 CFAP57 Zornitza Stark Phenotypes for gene: CFAP57 were changed from to Spermatogenic failure 95, MIM# 620917; Van der Woude Syndrome; Primary ciliary dyskinesia
Mendeliome v1.1958 CFAP57 Zornitza Stark Publications for gene: CFAP57 were set to
Mendeliome v1.1957 CFAP57 Zornitza Stark Classified gene: CFAP57 as Green List (high evidence)
Mendeliome v1.1957 CFAP57 Zornitza Stark Gene: cfap57 has been classified as Green List (High Evidence).
Mendeliome v1.1956 CFAP57 Zornitza Stark edited their review of gene: CFAP57: Added comment: PMID 36752199: 5 individuals from three families reported with biallelic LoF variants (two homozygous variants) and spermatogenic failure. Mouse model recapitulated the phenotype.; Changed rating: GREEN; Changed publications: 21574244, 32764743, 36752199; Changed phenotypes: Spermatogenic failure 95, MIM# 620917, Van der Woude Syndrome, Primary ciliary dyskinesia
Mendeliome v1.1259 CFAP20 Ain Roesley Marked gene: CFAP20 as ready
Mendeliome v1.1259 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Mendeliome v1.1259 CFAP20 Ain Roesley Phenotypes for gene: CFAP20 were changed from Retinitis pigmentosa (MONDO:0019200) to Retinitis pigmentosa (MONDO:0019200), CFAP20-related
Mendeliome v1.1258 CFAP20 Ain Roesley Classified gene: CFAP20 as Green List (high evidence)
Mendeliome v1.1258 CFAP20 Ain Roesley Gene: cfap20 has been classified as Green List (High Evidence).
Mendeliome v1.1254 CFAP20 Sarah Pantaleo gene: CFAP20 was added
gene: CFAP20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP20 were set to PMID:36329026
Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200)
Review for gene: CFAP20 was set to GREEN
Added comment: CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development.

Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy (retinitis pigments). Hence, CFAP20 functions within a structural./functional hub centred on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associaetd domains or macromolecular complexes.

Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin.

Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate.
Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5)
Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly).
Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys)

For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old).

Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues.
Sources: Literature
Mendeliome v0.14666 MFAP5 Elena Savva Marked gene: MFAP5 as ready
Mendeliome v0.14666 MFAP5 Elena Savva Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12641 SPAG7 Zornitza Stark Phenotypes for gene: SPAG7 were changed from to Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome, MONDO:0018540
Mendeliome v0.12637 SPAG7 Zornitza Stark reviewed gene: SPAG7: Rating: RED; Mode of pathogenicity: None; Publications: 24452265; Phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11991 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Mendeliome v0.11991 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Mendeliome v0.11991 TFAP2B Zornitza Stark Publications for gene: TFAP2B were set to 11505339; 15684060; 18752453; 21643846
Mendeliome v0.11990 TFAP2B Zornitza Stark edited their review of gene: TFAP2B: Changed publications: 31292255, 11505339, 15684060, 18752453, 21643846; Changed phenotypes: Char syndrome, MIM# 169100, Patent ductus arteriosus 2, MIM# 617035, Syndromic craniosynostosis
Mendeliome v0.11990 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035 to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035; Syndromic craniosynostosis
Mendeliome v0.11989 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035
Mendeliome v0.11988 TFAP2B Zornitza Stark Publications for gene: TFAP2B were set to
Mendeliome v0.11987 TFAP2B Zornitza Stark Mode of inheritance for gene: TFAP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11986 TFAP2B Zornitza Stark reviewed gene: TFAP2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 11505339, 15684060, 18752453, 21643846; Phenotypes: Char syndrome, MIM# 169100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10188 CFAP65 Zornitza Stark Publications for gene: CFAP65 were set to 31501240; 31413122
Mendeliome v0.10181 CFAP65 Eleanor Williams reviewed gene: CFAP65: Rating: ; Mode of pathogenicity: None; Publications: 34231842; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.9818 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from to Osteogenesis imperfecta, type XIX, (MIM301014); IFAP syndrome with or without BRESHECK syndrome (MIM#308205); Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800); Olmsted syndrome, X-linked (MIM#300918)
Mendeliome v0.9779 MBTPS2 Daniel Flanagan reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380894, 19361614, 21426410; Phenotypes: Osteogenesis imperfecta, type XIX, (MIM301014), IFAP syndrome with or without BRESHECK syndrome (MIM#308205), Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800), ?Olmsted syndrome, X-linked (MIM#300918); 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 v0.9690 CFAP45 Zornitza Stark Phenotypes for gene: CFAP45 were changed from Situs inversus; asthenospermia to Heterotaxy, visceral, 11, autosomal, with male infertility, MIM#619608
Mendeliome v0.9689 CFAP45 Zornitza Stark edited their review of gene: CFAP45: Changed phenotypes: Heterotaxy, visceral, 11, autosomal, with male infertility, MIM#619608
Mendeliome v0.9689 CFAP52 Zornitza Stark Phenotypes for gene: CFAP52 were changed from Heterotaxy to Heterotaxy, visceral, 10, autosomal, with male infertility, MIM#619607
Mendeliome v0.9688 CFAP52 Zornitza Stark edited their review of gene: CFAP52: Changed phenotypes: Heterotaxy, visceral, 10, autosomal, with male infertility, MIM#619607
Mendeliome v0.9319 CFAP221 Zornitza Stark Marked gene: CFAP221 as ready
Mendeliome v0.9319 CFAP221 Zornitza Stark Gene: cfap221 has been classified as Red List (Low Evidence).
Mendeliome v0.9319 CFAP221 Zornitza Stark gene: CFAP221 was added
gene: CFAP221 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP221 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP221 were set to 31636325
Phenotypes for gene: CFAP221 were set to Primary ciliary dyskinesia
Review for gene: CFAP221 was set to RED
Added comment: WES in 1 family with 3 siblings with clinical symptoms of PCD identified compound heterozygous loss-of-function variants in CFAP221, which segregated with disease. No functional studies. Nasal epithelial cells from 1 of the subjects demonstrated slightly reduced beat frequency, however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. A candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal.
Sources: Literature
Mendeliome v0.9075 CFAP206 Seb Lunke Marked gene: CFAP206 as ready
Mendeliome v0.9075 CFAP206 Seb Lunke Gene: cfap206 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9074 CFAP206 Seb Lunke Publications for gene: CFAP206 were set to
Mendeliome v0.9071 CFAP206 Seb Lunke Classified gene: CFAP206 as Amber List (moderate evidence)
Mendeliome v0.9071 CFAP206 Seb Lunke Gene: cfap206 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9070 CFAP206 Seb Lunke Phenotypes for gene: CFAP206 were changed from Multiple morphological abnormalities of the fagella to Multiple morphological abnormalities of the flagella
Mendeliome v0.9067 CFAP206 Ain Roesley gene: CFAP206 was added
gene: CFAP206 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP206 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFAP206 were set to Multiple morphological abnormalities of the fagella
Penetrance for gene: CFAP206 were set to unknown
Review for gene: CFAP206 was set to AMBER
Added comment: 1x hom with a fs variant

Sperm from knockout mouse model mainly had a fagellum of normal length but most of them showed abnormal forms including bent and coiled fagella. There was also a significant increase of sperm cells with absent or short fagella compared to the WT mice.
Sources: Literature
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 v0.7246 MFAP5 Zornitza Stark Phenotypes for gene: MFAP5 were changed from to Aortic aneurysm, familial thoracic MIM# 616166; MONDO:0014514
Mendeliome v0.7245 MFAP5 Zornitza Stark Publications for gene: MFAP5 were set to
Mendeliome v0.7244 MFAP5 Zornitza Stark Mode of inheritance for gene: MFAP5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7243 MFAP5 Zornitza Stark Classified gene: MFAP5 as Amber List (moderate evidence)
Mendeliome v0.7243 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7242 MFAP5 Zornitza Stark reviewed gene: MFAP5: Rating: AMBER; Mode of pathogenicity: None; Publications: 25434006, 30763214, 33807627, 33514025, 29524629; Phenotypes: Aortic aneurysm, familial thoracic MIM# 616166; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6404 CFAP47 Zornitza Stark Phenotypes for gene: CFAP47 were changed from asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF) to Spermatogenic failure, X-linked, 3, MIM# 301059; asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF)
Mendeliome v0.6403 CFAP47 Zornitza Stark edited their review of gene: CFAP47: Changed phenotypes: Spermatogenic failure, X-linked, 3, MIM# 301059
Mendeliome v0.6181 CFAP47 Zornitza Stark edited their review of gene: CFAP47: Changed rating: GREEN
Mendeliome v0.6181 CFAP47 Zornitza Stark Marked gene: CFAP47 as ready
Mendeliome v0.6181 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Green List (High Evidence).
Mendeliome v0.6181 CFAP47 Zornitza Stark Classified gene: CFAP47 as Green List (high evidence)
Mendeliome v0.6181 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Green List (High Evidence).
Mendeliome v0.6171 CFAP47 Hazel Phillimore gene: CFAP47 was added
gene: CFAP47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP47 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CFAP47 were set to PMID: 33472045
Phenotypes for gene: CFAP47 were set to asthenoteratozoospermia; morphological abnormalities of the flagella (MMAF)
Review for gene: CFAP47 was set to AMBER
Added comment: CFAP47 also known as CXorf22. 3 different missense variants in 3 unrelated Chinese individuals with asthenoteratozoospermia associated with morphological abnormalities of the flagella (MMAF). Immunoblotting and immunofluorescence showed reduced levels of CFAP47 in spermatozoa in all 3 men. A separate asthenoteratozoospermia cohort showed 1 individual with CNV including whole gene deletion of CFAP47.
Mouse model (with frameshift variants generated (via CRISPR-Cas9 technology) were sterile and presented with reduced sperm motility and abnormal flagellar morphology.
Sources: Literature
Mendeliome v0.5893 CFAP58 Zornitza Stark Phenotypes for gene: CFAP58 were changed from Multiple morphological abnormalities of the sperm flagella (MMAF) to Spermatogenic failure 49, MIM#619144; Multiple morphological abnormalities of the sperm flagella (MMAF)
Mendeliome v0.5892 CFAP58 Zornitza Stark reviewed gene: CFAP58: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 49, MIM#619144; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5592 CFAP52 Zornitza Stark Marked gene: CFAP52 as ready
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5592 CFAP52 Zornitza Stark Classified gene: CFAP52 as Green List (high evidence)
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Marked gene: CFAP45 as ready
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Classified gene: CFAP45 as Green List (high evidence)
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5576 CFAP52 Zornitza Stark gene: CFAP52 was added
gene: CFAP52 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP52 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP52 were set to 25469542; 33139725
Phenotypes for gene: CFAP52 were set to Heterotaxy
Review for gene: CFAP52 was set to GREEN
Added comment: Five unrelated families and functional data.
Sources: Literature
Mendeliome v0.5575 CFAP45 Zornitza Stark gene: CFAP45 was added
gene: CFAP45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP45 were set to 33139725
Phenotypes for gene: CFAP45 were set to Situs inversus; asthenospermia
Review for gene: CFAP45 was set to GREEN
Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5191 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5190 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5189 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979
Mendeliome v0.5188 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979
Mendeliome v0.4993 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016 to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mucoepithelial dysplasia, hereditary, MIM#158310
Mendeliome v0.4991 SREBF1 Zornitza Stark edited their review of gene: SREBF1: Added comment: HMD phenotype: 5 unrelated families reported with heterozygous variants at same residue (p.Arg557Cys and p.Arg557His) and a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Individuals developed cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses.; Changed publications: 32497488, 31790666, 32902915; Changed phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016, Mucoepithelial dysplasia, hereditary, MIM#158310
Mendeliome v0.4309 SREBF1 Zornitza Stark Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016
Mendeliome v0.4308 SREBF1 Zornitza Stark reviewed gene: SREBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome 2, MIM619016; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4262 CFAP58 Zornitza Stark Phenotypes for gene: CFAP58 were changed from Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035) to Multiple morphological abnormalities of the sperm flagella (MMAF)
Mendeliome v0.4261 CFAP58 Zornitza Stark Marked gene: CFAP58 as ready
Mendeliome v0.4261 CFAP58 Zornitza Stark Gene: cfap58 has been classified as Green List (High Evidence).
Mendeliome v0.4261 CFAP58 Zornitza Stark Classified gene: CFAP58 as Green List (high evidence)
Mendeliome v0.4261 CFAP58 Zornitza Stark Gene: cfap58 has been classified as Green List (High Evidence).
Mendeliome v0.4256 CFAP58 Crystle Lee edited their review of gene: CFAP58: Added comment: Biallelic variants reported in 5 unrelated males with nultiple morphological abnormalities of the sperm flagella (MMAF). Knockout mice were infertile.; Changed rating: GREEN; Changed publications: 32791035; Changed phenotypes: Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035); Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4256 CFAP58 Crystle Lee commented on gene: CFAP58
Mendeliome v0.4251 CFAP57 Zornitza Stark Mode of inheritance for gene: CFAP57 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 CFAP57 Zornitza Stark reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: 21574244, 32764743; Phenotypes: Van der Woude Syndrome, Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4250 CFAP58 Crystle Lee gene: CFAP58 was added
gene: CFAP58 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CFAP58 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP58 were set to 32791035
Phenotypes for gene: CFAP58 were set to Multiple morphological abnormalities of the sperm flagella (MMAF) (PMID: 32791035)
Review for gene: CFAP58 was set to AMBER
Added comment: 5 unrelated males reported with biallelic loss of function variants. Knockout mice were infertile (Abstract only)
Sources: Expert Review
Mendeliome v0.3251 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3251 CFAP74 Zornitza Stark Classified gene: CFAP74 as Amber List (moderate evidence)
Mendeliome v0.3251 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3250 CFAP74 Zornitza Stark gene: CFAP74 was added
gene: CFAP74 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP74 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP74 were set to 32555313
Phenotypes for gene: CFAP74 were set to Primary ciliary dyskinesia; infertility
Review for gene: CFAP74 was set to AMBER
Added comment: Two unrelated individuals with compound het missense variants reported.
Sources: Literature
Mendeliome v0.3242 SREBF1 Paul De Fazio gene: SREBF1 was added
gene: SREBF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SREBF1 were set to 32497488
Phenotypes for gene: SREBF1 were set to IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome
Review for gene: SREBF1 was set to GREEN
gene: SREBF1 was marked as current diagnostic
Added comment: 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. 3 different msisense variants identified affecting the same region (residues 527, 528, and 530). Functional studies support impaired function (impaired nuclear translocation of the transcriptionally active form of SREBP1 resulting in lower expression of the SREBP1 variants). Increased keratinocyte apoptosis was observed in patient scalp samples.
Sources: Literature
Mendeliome v0.2894 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
Mendeliome v0.2894 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Green List (High Evidence).
Mendeliome v0.2894 TFAP2A Zornitza Stark Phenotypes for gene: TFAP2A were changed from to Branchiooculofacial syndrome, MIM 113620
Mendeliome v0.2893 TFAP2A Zornitza Stark Publications for gene: TFAP2A were set to
Mendeliome v0.2892 TFAP2A Zornitza Stark Mode of pathogenicity for gene: TFAP2A was changed from to Other
Mendeliome v0.2891 TFAP2A Zornitza Stark Mode of inheritance for gene: TFAP2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2890 TFAP2A Teresa Zhao reviewed gene: TFAP2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 23578821, 21204207, 21728810, 21539471; Phenotypes: Branchiooculofacial syndrome, MIM 113620; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2750 CFAP53 Zornitza Stark Marked gene: CFAP53 as ready
Mendeliome v0.2750 CFAP53 Zornitza Stark Gene: cfap53 has been classified as Green List (High Evidence).
Mendeliome v0.2750 CFAP53 Zornitza Stark Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive 614779
Mendeliome v0.2749 CFAP53 Zornitza Stark Publications for gene: CFAP53 were set to
Mendeliome v0.2748 CFAP53 Zornitza Stark Mode of inheritance for gene: CFAP53 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2747 CFAP53 Zornitza Stark reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 28621423, 22577226, 26531781; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive 614779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2743 CFAP43 Zornitza Stark Marked gene: CFAP43 as ready
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v0.2743 CFAP43 Zornitza Stark Classified gene: CFAP43 as Green List (high evidence)
Mendeliome v0.2743 CFAP43 Zornitza Stark Gene: cfap43 has been classified as Green List (High Evidence).
Mendeliome v0.2742 CFAP43 Elena Savva gene: CFAP43 was added
gene: CFAP43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP43 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CFAP43 were set to PMID: 31884020; 28552195; 31004071; 29449551
Phenotypes for gene: CFAP43 were set to Hydrocephalus, normal pressure, 1 236690; Spermatogenic failure 19 617592
Added comment: aka WDR96

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

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

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

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

Summary: single report of AD hydrocephaly
Sources: Literature
Mendeliome v0.2629 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2625 ALPK1 Zornitza Stark changed review comment from: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature; to: Three unrelated families reported with PFAPA phenotype. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Mendeliome v0.2625 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache
Mendeliome v0.2583 ALPK1 Zornitza Stark gene: ALPK1 was added
gene: ALPK1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to 31053777
Phenotypes for gene: ALPK1 were set to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Review for gene: ALPK1 was set to AMBER
Added comment: Three unrelated families reported. One of the variants segregated in four affected individuals in one family and another was found to be de novo. The third variant however was not segregated, and is also present in 18 individuals in gnomad. Hence the evidence for variant pathogenicity in this third case is not compelling.
Sources: Literature
Mendeliome v0.2512 CFAP69 Zornitza Stark Marked gene: CFAP69 as ready
Mendeliome v0.2512 CFAP69 Zornitza Stark Gene: cfap69 has been classified as Green List (High Evidence).
Mendeliome v0.2512 CFAP69 Zornitza Stark Phenotypes for gene: CFAP69 were changed from to Asthenoteratospermia (Impaired sperm motility; severe flagellar abnormalities (short, coiled, absent or irregular calibre))
Mendeliome v0.2511 CFAP69 Zornitza Stark Publications for gene: CFAP69 were set to
Mendeliome v0.2510 CFAP69 Zornitza Stark Mode of inheritance for gene: CFAP69 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2428 GFAP Zornitza Stark Marked gene: GFAP as ready
Mendeliome v0.2428 GFAP Zornitza Stark Gene: gfap has been classified as Green List (High Evidence).
Mendeliome v0.2428 GFAP Zornitza Stark Phenotypes for gene: GFAP were changed from to Alexander disease, MIM# 203450
Mendeliome v0.2427 GFAP Zornitza Stark Publications for gene: GFAP were set to
Mendeliome v0.2426 GFAP Zornitza Stark Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2416 CFAP69 Ee Ming Wong reviewed gene: CFAP69: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29606301, 30415212; Phenotypes: Asthenoteratospermia (Impaired sperm motility, severe flagellar abnormalities (short, coiled, absent or irregular calibre)); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.2412 CFAP65 Zornitza Stark Marked gene: CFAP65 as ready
Mendeliome v0.2412 CFAP65 Zornitza Stark Gene: cfap65 has been classified as Green List (High Evidence).
Mendeliome v0.2412 CFAP65 Zornitza Stark Classified gene: CFAP65 as Green List (high evidence)
Mendeliome v0.2412 CFAP65 Zornitza Stark Gene: cfap65 has been classified as Green List (High Evidence).
Mendeliome v0.2368 GFAP Paul De Fazio reviewed gene: GFAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11138011, 12034785, 31004048, 15732097; Phenotypes: Leukodystrophy, macrocephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.2364 CFAP65 Daniel Flanagan gene: CFAP65 was added
gene: CFAP65 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP65 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP65 were set to 31501240; 31413122
Phenotypes for gene: CFAP65 were set to Spermatogenic failure 40 618664
Penetrance for gene: CFAP65 were set to unknown
Review for gene: CFAP65 was set to GREEN
gene: CFAP65 was marked as current diagnostic
Added comment: 9 patients with multiple morphological abnormalities of the sperm flagella (MMAF) or completely immotile spermatozoa, in which, homozygous or compound heterozygous truncating CFAP65 variants were identified. Cfap65-mutated male mice displayed typical MMAF phenotypes with severe morphological abnormalities of the sperm flagella (PMID: 31501240, 31413122).
Sources: Literature
Mendeliome v0.146 CFAP57 Sebastian Lunke Classified gene: CFAP57 as Amber List (moderate evidence)
Mendeliome v0.146 CFAP57 Sebastian Lunke Gene: cfap57 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.145 CFAP57 Sebastian Lunke Marked gene: CFAP57 as ready
Mendeliome v0.145 CFAP57 Sebastian Lunke Gene: cfap57 has been classified as Green List (High Evidence).
Mendeliome v0.145 CFAP57 Sebastian Lunke reviewed gene: CFAP57: Rating: AMBER; Mode of pathogenicity: None; Publications: bioRxiv 773028, doi: https://doi.org/10.1101/773028; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.0 TFAP2B Zornitza Stark gene: TFAP2B was added
gene: TFAP2B was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TFAP2B was set to Unknown
Mendeliome v0.0 TFAP2A Zornitza Stark gene: TFAP2A was added
gene: TFAP2A was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TFAP2A was set to Unknown
Mendeliome v0.0 MFAP5 Zornitza Stark gene: MFAP5 was added
gene: MFAP5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MFAP5 was set to Unknown
Mendeliome v0.0 GFAP Zornitza Stark gene: GFAP was added
gene: GFAP was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GFAP was set to Unknown
Mendeliome v0.0 CFAP69 Zornitza Stark gene: CFAP69 was added
gene: CFAP69 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CFAP69 was set to Unknown
Mendeliome v0.0 CFAP57 Zornitza Stark gene: CFAP57 was added
gene: CFAP57 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CFAP57 was set to Unknown
Mendeliome v0.0 CFAP53 Zornitza Stark gene: CFAP53 was added
gene: CFAP53 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CFAP53 was set to Unknown