ClinVar Miner

Submissions for variant NM_000082.3(ERCC8):c.399+1G>A (rs774047625)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664613 SCV000788607 likely pathogenic Cockayne syndrome type A 2017-04-28 criteria provided, single submitter clinical testing
Invitae RCV001378262 SCV001575797 likely pathogenic not provided 2020-10-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the ERCC8 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 ERCC8 are known to be pathogenic (PMID: 29572252). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with Cockayne syndrome (PMID: 16865293). It is also known as IVS4+1G>A. ClinVar contains an entry for this variant (Variation ID: 550005). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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