Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813006 | SCV000953339 | pathogenic | Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia | 2023-08-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 656557). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala147Cysfs*28) in the SLC26A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A2 are known to be pathogenic (PMID: 7923357, 10482955, 11241838). |
| Baylor Genetics | RCV003472418 | SCV004201754 | likely pathogenic | Achondrogenesis, type IB | 2023-08-19 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV004576972 | SCV005060900 | likely pathogenic | Atelosteogenesis type II | criteria provided, single submitter | clinical testing | The observed frameshift c.438dup(p.Ala147CysfsTer28) variant in SLC26A2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with an allele frequency of 0.0008% in gnomAD Exomes database. This variant has been submitted to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Alanine 147, changes this amino acid to Cysteine residue, and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Ala147CysfsTer28. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. Functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic. In absence of another reportable variant in SLC26A2 gene, the molecular diagnosis is not confirmed. |