ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.2830-2A>G (rs373227647)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000170381 SCV000222798 pathogenic Cockayne syndrome B 2012-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000397640 SCV000329643 pathogenic not provided 2016-07-19 criteria provided, single submitter clinical testing The c.2830-2A>G pathogenic variant in the ERCC6 gene has been reported previously in two unrelated individuals with congenital Cockayne syndrome (Frouin et al., 2013; Laugel et al., 2010). This splice site variant destroys the canonical splice acceptor site in intron 15. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2830-2A>G variant was not observed in the homozgyous state or at any significant frequency in approximately 6500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. We interpret c.2830-2A>G as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000762809 SCV000893160 pathogenic DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome B; Lung cancer; UV-sensitive syndrome 1; Age-related macular degeneration 5; Premature ovarian failure 11 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000397640 SCV001405205 pathogenic not provided 2019-11-12 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 15 of the ERCC6 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs373227647, ExAC 0.003%). This variant has been observed in individual(s) with Cockayne syndrome (PMID: 19894250, 24154677). ClinVar contains an entry for this variant (Variation ID: 190163). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 19894250). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 9443879, 18628313). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000984002 SCV000792730 pathogenic DE SANCTIS-CACCHIONE SYNDROME 2017-07-13 no assertion criteria provided clinical testing

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