ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.1606G>A (p.Val536Met)

gnomAD frequency: 0.00026  dbSNP: rs142568756
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001132704 SCV001292372 uncertain significance Xeroderma pigmentosum, group D 2017-04-28 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001360953 SCV001556909 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 536 of the ERCC2 protein (p.Val536Met). This variant is present in population databases (rs142568756, gnomAD 0.03%). This missense change has been observed in individual(s) with breast cancer (PMID: 27504877). ClinVar contains an entry for this variant (Variation ID: 893766). 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 expected to disrupt ERCC2 protein function. Experimental studies have shown that this missense change affects ERCC2 function (PMID: 27504877). 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.
Sema4, Sema4 RCV002255623 SCV002531562 uncertain significance Xeroderma pigmentosum 2021-12-21 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002482256 SCV002789001 uncertain significance Cerebrooculofacioskeletal syndrome 2; Xeroderma pigmentosum, group D; Trichothiodystrophy 1, photosensitive 2022-04-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001360953 SCV003833565 uncertain significance not provided 2020-01-30 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596410 SCV005089930 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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