ClinVar Miner

Submissions for variant NM_012463.4(ATP6V0A2):c.1514+1G>A

gnomAD frequency: 0.00001  dbSNP: rs374480381
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174367 SCV000225655 pathogenic not provided 2012-08-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002498429 SCV002808753 pathogenic Cutis laxa with osteodystrophy; Wrinkly skin syndrome 2022-05-17 criteria provided, single submitter clinical testing
GeneDx RCV000174367 SCV004035665 likely pathogenic not provided 2023-08-31 criteria provided, single submitter clinical testing Has been reported in an individual with autosomal recessive cutis laxa who also harbored another ATP6V0A2 variant (Hucthagowder et al., 2009).; Identified in an individual referred for testing for congenital disorders of glycosylation who was heterozygous for a deletion of exon 9 of the ATP6V0A2 gene (Jones et al., 2013).; The c.1514+1G>A variant was reported in the homozygous state in a 13 year-old female undergoing whole exome sequencing for primary immunodeficiency diseases characterized as lymphoproliferative or NK cell defect (Stray-Pedersen et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 23806237, 27577878, 19321599, 33369135)
Labcorp Genetics (formerly Invitae), Labcorp RCV003502514 SCV004295443 pathogenic ALG9 congenital disorder of glycosylation 2023-09-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 12 of the ATP6V0A2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP6V0A2 are known to be pathogenic (PMID: 18157129, 19321599). This variant is present in population databases (rs374480381, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with Cutis laxa (PMID: 19321599). ClinVar contains an entry for this variant (Variation ID: 95519). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.