Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174852 | SCV001338242 | uncertain significance | not specified | 2020-02-02 | criteria provided, single submitter | clinical testing | Variant summary: ADAMTS2 c.3088+15G>A 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 8.6e-05 in 150452 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ADAMTS2 causing Ehlers-Danlos Syndrome, Type VIIC (Dermatosparaxis) (8.6e-05 vs 0.0029), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3088+15G>A in individuals affected with Ehlers-Danlos Syndrome, Type VIIC (Dermatosparaxis) and no experimental evidence demonstrating its impact on protein function have 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 uncertain significance. |
Invitae | RCV002067866 | SCV002391688 | likely benign | Ehlers-Danlos syndrome, dermatosparaxis type | 2023-10-14 | criteria provided, single submitter | clinical testing |