Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756062 | SCV000883775 | uncertain significance | not provided | 2017-06-08 | criteria provided, single submitter | clinical testing | One copy of a variant of uncertain significance, c.9505A>G; p.Ile3169Val, was detected in the DYNC2H1 gene by massively parallel sequencing and confirmed by Sanger sequencing. The p.Ile3169Val variant (rs200170585) has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. This variant is listed in the Exome Variant Server (EVS) with an overall allele frequency 0.11% (identified in 13 out of 11,870 chromosomes), and in the ExAC browser with an overall frequency 0.05% (identified in 14 out of 30,434 chromosomes). The isoleucine at codon 3169 is highly conserved considering 28 species up to C. elegans (Alamut software v2.7.1), although computational prediction programs return mixed results regarding impact of this variant on DYNC2H1 protein structure/function (SIFT: damaging, PolyPhen2: benign, MutationTaster: disease causing). Thus, based on the available information, the clinical significance of the p.Ile3169Val variant cannot be determined with certainty. |
| Labcorp Genetics |
RCV001089328 | SCV001129634 | likely benign | Jeune thoracic dystrophy | 2025-01-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222621 | SCV002500796 | likely benign | not specified | 2022-03-31 | criteria provided, single submitter | clinical testing | Variant summary: DYNC2H1 c.9505A>G (p.Ile3169Val) results in a conservative amino acid change located in the Dynein heavy chain, coiled coil stalk domain (IPR024743) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 189026 control chromosomes, predominantly at a frequency of 0.0032 within the African or African-American subpopulation in the gnomAD database. This frequency does not allow conclusions about variant significance although the frequency seems higher than would be expected for an early onset phenotypic presentation. To our knowledge, no occurrence of c.9505A>G in individuals affected with Short-Rib Thoracic Dysplasia 3 With Or Without Polydactyly and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002536558 | SCV003608423 | uncertain significance | Inborn genetic diseases | 2024-03-30 | criteria provided, single submitter | clinical testing | The c.9505A>G (p.I3169V) alteration is located in exon 61 (coding exon 61) of the DYNC2H1 gene. This alteration results from a A to G substitution at nucleotide position 9505, causing the isoleucine (I) at amino acid position 3169 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |