Submissions for variant NM_000053.4(ATP7B):c.2795C>A (p.Ser932Ter)

dbSNP: rs1566498495

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780939	SCV000918609	pathogenic	Wilson disease	2018-12-14	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.2795C>A (p.Ser932X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.3083_3085delinsG/p.Lys1028fsX40, c.3402delC/p.Ala1135fsX13). The variant was absent in 246110 control chromosomes. c.2795C>A has been reported in the literature in multiple individuals affected with Wilson Disease (Deguti_2004, Margarit_2005). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Mendelics	RCV000780939	SCV001139353	pathogenic	Wilson disease	2019-05-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000780939	SCV001977305	pathogenic	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
DASA	RCV000780939	SCV002107140	pathogenic	Wilson disease	2022-03-05	criteria provided, single submitter	clinical testing	The c.2795C>A;p.(Ser932*) variant creates a premature translational stop signal in the ATP7B gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 633075; PMID: 15024742; PMID: 15952988) - PS4. This variant is not present in population databases (rs1566498495- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The p.(Ser932*) was detected in trans with a pathogenic variant (PMID: 15024742; PMID: 15952988) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic
Fulgent Genetics, Fulgent Genetics	RCV000780939	SCV002809345	pathogenic	Wilson disease	2021-12-15	criteria provided, single submitter	clinical testing
Invitae	RCV000780939	SCV003442175	pathogenic	Wilson disease	2023-02-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser932*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 15024742, 15952988). ClinVar contains an entry for this variant (Variation ID: 633075). 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.
Natera, Inc.	RCV000780939	SCV002086844	pathogenic	Wilson disease	2021-07-27	no assertion criteria provided	clinical testing