ClinVar Miner

Submissions for variant NM_005236.3(ERCC4):c.1197_1198insCA (p.Ala400fs)

dbSNP: rs779091652
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001781048 SCV002024504 likely pathogenic not provided 2019-06-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003772149 SCV004593897 pathogenic Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q 2023-08-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala400Glnfs*10) in the ERCC4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC4 are known to be pathogenic (PMID: 9580660). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1324343). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. This variant is present in population databases (rs779091652, gnomAD 0.003%).
Genetic Services Laboratory, University of Chicago RCV001781048 SCV003839478 likely pathogenic not provided 2022-10-20 no assertion criteria provided clinical testing DNA sequence analysis of the ERCC4 gene demonstrated a 2 base pair insertion in exon 7, c.1197_1198insCA. This likely pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 10 amino acids downstream of the change, p.Ala400Glnfs*10. This likely pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ERCC4 protein with potentially abnormal function. This sequence change has been described in the gnomAD database in 3 individuals which corresponds to a population frequency of 0.0012% (dbSNP rs779091652). While this insertion has not previously been described in the literature, other frameshift and truncating variants in the ERCC4 gene have been described in individuals with ERCC4-related disorders (PMID: 9580660, 29892709). Based on these evidences this variant is interpreted as likely pathogenic.

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