ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.183+2T>A

gnomAD frequency: 0.00004  dbSNP: rs201127596
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000260066 SCV000413594 likely pathogenic Xeroderma pigmentosum, group D 2024-06-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001859951 SCV002243467 pathogenic not provided 2024-11-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the ERCC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC2 are known to be pathogenic (PMID: 9238033, 11335038, 19085937, 19934020). This variant is present in population databases (rs201127596, gnomAD 0.007%). Disruption of this splice site has been observed in individual(s) with xeroderma pigmentosum (PMID: 7585650). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 329529). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000260066 SCV003806820 likely pathogenic Xeroderma pigmentosum, group D 2022-12-09 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 strong, PM2 moderated
GeneDx RCV001859951 SCV004025509 likely pathogenic not provided 2023-08-09 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 7585650)
Baylor Genetics RCV003470317 SCV004194676 pathogenic Cerebrooculofacioskeletal syndrome 2 2023-11-14 criteria provided, single submitter clinical testing

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