Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000547108 | SCV000651657 | likely benign | Charcot-Marie-Tooth disease axonal type 2O | 2023-10-06 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002367929 | SCV002658544 | likely benign | Inborn genetic diseases | 2021-05-26 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330790 | SCV004038802 | uncertain significance | not specified | 2023-08-22 | criteria provided, single submitter | clinical testing | Variant summary: DYNC1H1 c.6406-4G>C 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 8.8e-05 in 250976 control chromosomes, predominantly at a frequency of 0.00019 within the Non-Finnish European subpopulation in the gnomAD database. To our knowledge, no occurrence of c.6406-4G>C in individuals affected with DYNC1H1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |