ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.1009A>T (p.Lys337Ter)

dbSNP: rs1198241866
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665546 SCV000789688 likely pathogenic DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 2017-02-09 criteria provided, single submitter clinical testing
Invitae RCV000809201 SCV000949344 pathogenic not provided 2021-08-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV001449817 SCV001653117 pathogenic Cockayne syndrome type 2 2021-02-22 criteria provided, single submitter clinical testing The p.Lys337X variant in ERCC6 has been reported in a compound heterozygous state in an individual with Cockayne syndrome, who carried a second pathogenic variant in ERCC6 (Troelstra 1992 PMID: 1339317, Schmickel 1977 PMID: 887325). It has also been identified in 1/113716 European chromosomes by gnomAD ( and reported in ClinVar (Variation ID 550722). This nonsense variant leads to a premature termination codon at position 337, which is predicted to lead to a truncated or absent protein. Loss of function of the ERCC6 gene is an established disease mechanism in autosomal recessive Cockayne syndrome. An animal model in ERCC6 has shown that a similar variant causes some features of Cockayne Syndrome including photosensitivity, but only mild deficits in growth and neurologic function (van Der Horst 1997 PMID: 9150142). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Cockayne syndrome. ACMG/AMP criteria applied: PVS1, PM2_Suporting, PM3, PS3_Moderate.

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