Submissions for variant NM_000112.4(SLC26A2):c.1724del (p.Lys575fs)

dbSNP: rs386833498

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586135	SCV000695417	pathogenic	Sulfate transporter-related osteochondrodysplasia	2017-01-26	criteria provided, single submitter	clinical testing	Variant summary: The SLC26A2 c.1724delA (p.Lys575Serfs) variant results in a premature termination codon, predicted to cause a truncated or absent SLC26A2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121446 control chromosomes. This variant has been reported in multiple affected individuals and classified as pathogenic/likely pathogenic by clinical diagnostic laboratories and reputable databases. Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817526	SCV000958092	pathogenic	Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys575Serfs*10) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 165 amino acid(s) of the SLC26A2 protein. This variant is present in population databases (rs749382145, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with achondrogenesis, atelosteogenesis, and diastrophic dysplasia (PMID: 7923357, 8528239, 8571951; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 4087). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002276529	SCV002567001	pathogenic	Connective tissue disorder	2019-05-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000817526	SCV002805764	pathogenic	Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia	2021-08-16	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000023567	SCV004201736	pathogenic	Achondrogenesis, type IB	2024-02-29	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000004302	SCV005374192	pathogenic	Diastrophic dysplasia	2024-09-22	criteria provided, single submitter	clinical testing
OMIM	RCV000004302	SCV000024468	pathogenic	Diastrophic dysplasia	1996-02-01	no assertion criteria provided	literature only
OMIM	RCV000004303	SCV000024470	pathogenic	Atelosteogenesis type II	1996-02-01	no assertion criteria provided	literature only
OMIM	RCV000023567	SCV000044858	pathogenic	Achondrogenesis, type IB	1996-02-01	no assertion criteria provided	literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000004302	SCV000081859	probable-pathogenic	Diastrophic dysplasia		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV000023567	SCV002026485	pathogenic	Achondrogenesis, type IB	2021-11-24	no assertion criteria provided	clinical testing	The homozygous frameshift deletion variant c.1724delA has been previously reported as c.1751delA by Superti-Furga A et al in 1996 in a Dutch patient. The allele frequency-0.0048% in gnomAD (aggregated) database and 0.0058% in 1000g. Phenotype observed in the proband was cystic hygroma, generalized subcutaneous edema with skin thickening, hypoechogenic area and distorted fetal limbs. Achondrogensis IB is an autosomal recessive disorder. Based on the phenotypic observation and the available literature, we classify this variant as pathogenic.
Natera, Inc.	RCV000023567	SCV002081861	pathogenic	Achondrogenesis, type IB	2020-10-15	no assertion criteria provided	clinical testing