ClinVar Miner

Submissions for variant NM_025132.4(WDR19):c.3703G>A (p.Glu1235Lys)

gnomAD frequency: 0.00001  dbSNP: rs587777351
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788500 SCV000927644 pathogenic not provided 2018-04-19 criteria provided, single submitter clinical testing
Molecular Biology Laboratory, Fundació Puigvert RCV001281118 SCV001425291 likely pathogenic Senior-Loken syndrome 8 2020-02-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001854544 SCV002232771 pathogenic Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1235 of the WDR19 protein (p.Glu1235Lys). This variant is present in population databases (rs587777351, gnomAD 0.009%). This missense change has been observed in individual(s) with WDR19-related conditions (PMID: 23559409, 25726036, 33532864). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 127157). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WDR19 protein function. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002477273 SCV002781796 likely pathogenic Asphyxiating thoracic dystrophy 5; Nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8; Spermatogenic failure 72 2022-04-07 criteria provided, single submitter clinical testing
3billion RCV000115013 SCV003842062 pathogenic Nephronophthisis 13 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.68; 3Cnet: 0.88). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000127157). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25726036). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 25726036). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM RCV000115013 SCV000148922 pathogenic Nephronophthisis 13 2013-08-01 no assertion criteria provided literature only

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