Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667661 | SCV000792147 | uncertain significance | Multiple epiphyseal dysplasia type 4 | 2017-06-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002530719 | SCV003439210 | uncertain significance | Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia | 2022-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 256 of the SLC26A2 protein (p.Phe256Ser). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with autosomal recessive multiple epiphyseal dysplasia (PMID: 21922596). ClinVar contains an entry for this variant (Variation ID: 552411). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC26A2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Baylor Genetics | RCV003472088 | SCV004201759 | likely pathogenic | Achondrogenesis, type IB | 2024-02-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689837 | SCV005184718 | uncertain significance | not specified | 2024-05-14 | criteria provided, single submitter | clinical testing | Variant summary: SLC26A2 c.767T>C (p.Phe256Ser) results in a non-conservative amino acid change located in the SLC26A/SulP transporter domain (IPR011547) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251356 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.767T>C has been reported in the literature in at least one compound heterozygous individual affected with multiple epiphyseal dysplasia. These data do not provide sufficient evidence to allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 552411). Based on the evidence outlined above, the variant was classified as uncertain significance. |