Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000128125 | SCV000171717 | benign | not specified | 2013-02-01 | 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. |
Invitae | RCV000205809 | SCV000262137 | benign | Arterial tortuosity syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000128125 | SCV000314728 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000205809 | SCV000434166 | benign | Arterial tortuosity syndrome | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
ARUP Laboratories, |
RCV000205809 | SCV000605157 | benign | Arterial tortuosity syndrome | 2023-11-09 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000205809 | SCV000743112 | benign | Arterial tortuosity syndrome | 2014-10-09 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000205809 | SCV000744124 | benign | Arterial tortuosity syndrome | 2017-05-31 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001171031 | SCV001333700 | benign | Familial thoracic aortic aneurysm and aortic dissection | 2019-04-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000128125 | SCV001372348 | benign | not specified | 2020-06-01 | criteria provided, single submitter | clinical testing | Variant summary: SLC2A10 c.1288+10G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: two predict the variant strengthens a cryptic 3' acceptor site; two predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.01 in 238094 control chromosomes in the gnomAD database, including 25 homozygotes. The observed variant frequency is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1288+10G>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign n=3, VUS n=1). Based on the evidence outlined above, the variant was classified as benign. |
Ambry Genetics | RCV001171031 | SCV002690835 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2015-08-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |