Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001104416 | SCV001261282 | uncertain significance | Asphyxiating thoracic dystrophy 3 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV001248024 | SCV001421483 | likely benign | Jeune thoracic dystrophy | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002558043 | SCV003716618 | uncertain significance | Inborn genetic diseases | 2021-09-17 | criteria provided, single submitter | clinical testing | The c.6769G>A (p.G2257S) alteration is located in exon 42 (coding exon 42) of the DYNC2H1 gene. This alteration results from a G to A substitution at nucleotide position 6769, causing the glycine (G) at amino acid position 2257 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV001358422 | SCV001554148 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The DYNC2H1 p.Gly2257Ser variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs199897162) and in control databases in 84 of 279860 chromosomes at a frequency of 0.0003002 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 80 of 127876 chromosomes (freq: 0.000626), Other in 2 of 7114 chromosomes (freq: 0.000281), African in 1 of 24188 chromosomes (freq: 0.000041) and South Asian in 1 of 30594 chromosomes (freq: 0.000033), but was not observed in the Latino, Ashkenazi Jewish, East Asian, or European (Finnish) populations. The p.Gly2257 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |