ClinVar Miner

Submissions for variant NM_012120.3(CD2AP):c.992T>A (p.Leu331His)

gnomAD frequency: 0.00074  dbSNP: rs140188898
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000378792 SCV000463769 likely benign Focal segmental glomerulosclerosis 3, susceptibility to 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV001295491 SCV001484416 uncertain significance not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 331 of the CD2AP protein (p.Leu331His). This variant is present in population databases (rs140188898, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CD2AP-related conditions. ClinVar contains an entry for this variant (Variation ID: 357171). 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 CD2AP protein function with a negative predictive value of 80%. 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.

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