Submissions for variant NM_000112.4(SLC26A2):c.906_907del (p.Leu302_Cys303insTer)

dbSNP: rs386833509

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003474631	SCV004201764	likely pathogenic	Achondrogenesis, type IB	2023-07-02	criteria provided, single submitter	clinical testing
Invitae	RCV003764720	SCV004569668	pathogenic	Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia	2023-07-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Ala715Val) have been determined to be pathogenic (PMID: 21077204). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 56029). This premature translational stop signal has been observed in individual(s) with skeletal dysplasia (PMID: 11241838). This variant is present in population databases (rs752197406, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Cys303*) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 437 amino acid(s) of the SLC26A2 protein.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049438	SCV000081871	probable-pathogenic	Diastrophic dysplasia		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.