Submissions for variant NM_000112.4(SLC26A2):c.1777G>T (p.Glu593Ter)

dbSNP: rs905644652

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001212481	SCV001384064	pathogenic	Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia	2019-10-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SLC26A2 protein. Other variant(s) that disrupt this region (p.Thr627Leufs*23) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with SLC26A2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SLC26A2 gene (p.Glu593*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 amino acids of the SLC26A2 protein.
PreventionGenetics, part of Exact Sciences	RCV004528418	SCV004110098	likely pathogenic	SLC26A2-related disorder	2023-06-08	criteria provided, single submitter	clinical testing	The SLC26A2 c.1777G>T variant is predicted to result in premature protein termination (p.Glu593*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in SLC26A2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics	RCV003473759	SCV004201797	likely pathogenic	Achondrogenesis, type IB	2022-09-23	criteria provided, single submitter	clinical testing