ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter)

dbSNP: rs72554640
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193235 SCV000246657 pathogenic Menkes kinky-hair syndrome 2013-02-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757017 SCV000885042 pathogenic not provided 2017-08-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000193235 SCV001338560 pathogenic Menkes kinky-hair syndrome 2020-04-03 criteria provided, single submitter clinical testing Variant summary: ATP7A c.1933C>T (p.Arg645X) 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. The variant was absent in 183238 control chromosomes (gnomAD). c.1933C>T has been reported in the literature in multiple individuals affected with Menkes kinky-hair syndrome (e.g. Das_1994, Hahn_2001, Mohamed_2015, Tumer_1997). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001271473 SCV002238921 pathogenic Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 2024-01-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg645*) in the ATP7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7A are known to be pathogenic (PMID: 11241493, 20652413). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ATP7A-related conditions (PMID: 7977350, 32005694). ClinVar contains an entry for this variant (Variation ID: 210404). 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.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000193235 SCV000844970 pathogenic Menkes kinky-hair syndrome 2018-09-18 no assertion criteria provided clinical testing The observed variant c.1933C>T has not been reported in 1000 Genomes and ExAC databases. The in silico prediction of the given variant is damaging by MutationTaster2 and LRT.
Natera, Inc. RCV001271473 SCV001452640 pathogenic Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 2020-09-16 no assertion criteria provided clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami RCV000193235 SCV004011996 uncertain significance Menkes kinky-hair syndrome 2016-01-06 no assertion criteria provided literature only

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