ClinVar Miner

Submissions for variant NM_002230.4(JUP):c.1054+7A>T

gnomAD frequency: 0.00049  dbSNP: rs371988639
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000214942 SCV000270292 likely benign not specified 2015-03-11 criteria provided, single submitter clinical testing c.1054+7A>T in intron 6 of JUP: This variant is not expected to have clinical si gnificance because it is not located within the splice consensus sequence. It ha s been identified in 5/10400 African chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs371988639).
Illumina Laboratory Services, Illumina RCV000341689 SCV000402738 uncertain significance Arrhythmogenic right ventricular dysplasia 12 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000404177 SCV000402739 uncertain significance Naxos disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000461949 SCV000560969 likely benign Naxos disease; Arrhythmogenic right ventricular dysplasia 12 2024-01-24 criteria provided, single submitter clinical testing
GeneDx RCV000214942 SCV000728582 likely benign not specified 2018-01-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001726048 SCV001473875 likely benign not provided 2020-01-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000214942 SCV001572532 benign not specified 2021-04-15 criteria provided, single submitter clinical testing Variant summary: JUP c.1054+7A>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 282628 control chromosomes, predominantly at a frequency of 0.0011 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 44 fold of the estimated maximal expected allele frequency for a pathogenic variant in JUP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1054+7A>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003150105 SCV003838889 likely benign Cardiomyopathy 2021-08-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003917896 SCV004732671 likely benign JUP-related disorder 2021-11-22 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center RCV000214942 SCV001922393 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001726048 SCV001965578 likely benign not provided no assertion criteria provided clinical testing

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.