Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204107 | SCV000260278 | pathogenic | Jeune thoracic dystrophy | 2015-08-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant was found in trans with a pathogenic variant in DYNC2H1 (c.1757T>G) in the proband of this family who was diagnosed with asphyxiating thoracic dystrophy. The phase of the two variants were confirmed through parental testing. While this particular variant has not been reported in the literature, truncating variants in DYNC2H1 are known to be pathogenic (PMID: 22499340, 23339108). This sequence change affects a donor splice site in intron 18. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330580 | SCV004037954 | likely pathogenic | Asphyxiating thoracic dystrophy 3 | 2023-08-02 | criteria provided, single submitter | clinical testing | Variant summary: DYNC2H1 c.2702+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 243666 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2702+1G>A in individuals affected with Short-rib thoracic dysplasia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |