ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.2824G>A (p.Gly942Ser)

gnomAD frequency: 0.00004  dbSNP: rs370336663
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001224786 SCV001397008 uncertain significance Cohen syndrome 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 942 of the VPS13B protein (p.Gly942Ser). This variant also falls at the last nucleotide of exon 19, which is part of the consensus splice site for this exon. This variant is present in population databases (rs370336663, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 952641). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Ambry Genetics RCV002563664 SCV003740388 uncertain significance Inborn genetic diseases 2021-06-22 criteria provided, single submitter clinical testing The c.2824G>A (p.G942S) alteration is located in exon 19 (coding exon 18) of the VPS13B gene. This alteration results from a G to A substitution at nucleotide position 2824, causing the glycine (G) at amino acid position 942 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001224786 SCV002079533 uncertain significance Cohen syndrome 2020-09-30 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004743335 SCV005364262 uncertain significance VPS13B-related disorder 2024-07-01 no assertion criteria provided clinical testing The VPS13B c.2824G>A variant is predicted to result in the amino acid substitution p.Gly942Ser. This variant also modifies the final nucleotide of exon 19, and is predicted to modestly reduce the efficiency of splicing (Alamut Visual v2.11). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0081% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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