ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.1267G>A (p.Asp423Asn)

gnomAD frequency: 0.00034  dbSNP: rs143710107
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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 RCV001323801 SCV001514731 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 423 of the ERCC2 protein (p.Asp423Asn). This variant is present in population databases (rs143710107, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023715). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001323801 SCV002009201 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002259105 SCV002531547 uncertain significance Xeroderma pigmentosum 2022-02-08 criteria provided, single submitter curation
Ambry Genetics RCV002545132 SCV003734548 uncertain significance Inborn genetic diseases 2021-07-27 criteria provided, single submitter clinical testing The c.1267G>A (p.D423N) alteration is located in exon 13 (coding exon 13) of the ERCC2 gene. This alteration results from a G to A substitution at nucleotide position 1267, causing the aspartic acid (D) at amino acid position 423 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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