Submissions for variant NM_015910.7(WDPCP):c.1448G>A (p.Arg483Gln)

gnomAD frequency: 0.00001  dbSNP: rs544657165

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000624967	SCV000743215	benign	Bardet-Biedl syndrome 1	2015-08-06	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000624967	SCV000744309	likely benign	Bardet-Biedl syndrome 1	2015-12-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001142952	SCV001303446	uncertain significance	Bardet-Biedl syndrome 15	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001319711	SCV001510469	uncertain significance	Bardet-Biedl syndrome	2022-08-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 483 of the WDPCP protein (p.Arg483Gln). This variant is present in population databases (rs544657165, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with WDPCP-related conditions. ClinVar contains an entry for this variant (Variation ID: 522195). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Endocrinology Laboratory, Christian Medical College	RCV001142952	SCV002073521	uncertain significance	Bardet-Biedl syndrome 15		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003411476	SCV004116105	uncertain significance	WDPCP-related disorder	2024-02-12	no assertion criteria provided	clinical testing	The WDPCP c.1448G>A variant is predicted to result in the amino acid substitution p.Arg483Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.072% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, the clinical significance of this variant is classified as uncertain at this time due to insufficient functional and genetic evidence.