ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.2167C>T (p.Gln723Ter) (rs151242354)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000170378 SCV000222793 pathogenic Cockayne syndrome B 2013-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000256036 SCV000321604 pathogenic not provided 2017-05-23 criteria provided, single submitter clinical testing The Q723X variant in the ERCC6 gene has been reported previously in congenital Cockayne syndrome, in an affected individual who was compound heterozygous for the Q723X variant and another ERCC6 mutation (Laugel et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q723X 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 Q723X as a pathogenic variant.
Baylor Genetics RCV000170378 SCV000807646 pathogenic Cockayne syndrome B 2017-09-01 criteria provided, single submitter clinical testing This mutation has been previously reported as disease-causing and was found twice in our laboratory in trans with another pathogenic mutation in patients, including one with suspected diagnosis of Cockayne syndrome. Heterozygotes are expected to be asymptomatic carriers.
Illumina Clinical Services Laboratory,Illumina RCV000778283 SCV000914459 pathogenic ERCC6-Related Disorders 2018-12-10 criteria provided, single submitter clinical testing The ERCC6 c.2167C>T (p.Gln723Ter) variant is a stop-gained in the splice region variant that is predicted to result in premature truncation of the protein. The p.Gln723Ter variant has been reported in two studies in which it is found in a total of 12 individuals affected with Cockayne syndrome-B, including in two in a homozygous state and in ten in a compound heterozygous state with a unique null variant (Laugel et al. 2010; Calmels et al. 2018). Control data are unavailable for this variant, which is reported at a frequency of 0.00047 in the European American population of the Exome Sequencing Project. The p.Gln723Ter variant has not been reported in the literature in association with macular degeneration or cerebrooculofacioskeletal syndrome. Based on the collective evidence and the potential impact of stop-gained variants, the p.Gln723Ter variant is classified as pathogenic for ERCC6-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000256036 SCV001233485 pathogenic not provided 2019-11-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln723*) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs151242354, ExAC 0.008%). This variant has been observed in an individual affected with Cockayne syndrome (PMID: 19894250). ClinVar contains an entry for this variant (Variation ID: 190160). 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 RCV000983999 SCV000792505 likely pathogenic DE SANCTIS-CACCHIONE SYNDROME 2017-06-26 no assertion criteria provided clinical testing

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