VCV002678883.3 - ClinVar

NM_000112.4(SLC26A2):c.822del (p.Leu275fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (1); Likely pathogenic (1)

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000112.4(SLC26A2):c.822del (p.Leu275fs)

Variation ID: 2678883 Accession: VCV002678883.3

Type and length

Deletion, 1 bp

Location

Cytogenetic: 5q32 5: 149980413 (GRCh38) [ NCBI UCSC ] 5: 149359976 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 30, 2023	Feb 23, 2026	Feb 15, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000112.4:c.822del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000103.2:p.Leu275fs	frameshift
NC_000005.10:g.149980415del
NC_000005.9:g.149359978del
NG_007147.2:g.21533del
LRG_684:g.21533del
LRG_684t1:c.822del	LRG_684p1:p.Leu275Serfs

... more HGVS ... less HGVS

Protein change

L275fs

Other names

Canonical SPDI

NC_000005.10:149980412:GGG:GG

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA2695198771 dbSNP: rs2480774313 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SLC26A2		-	-	GRCh38 GRCh37	946	969

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Achondrogenesis, type IB	Likely pathogenic (1)	criteria provided, single submitter	Aug 14, 2023	RCV003472859.1
Achondrogenesis, type IB Atelosteogenesis type II Diastrophic dysplasia Multiple epiphyseal dysplasia type 4	Pathogenic (1)	criteria provided, single submitter	Feb 15, 2025	RCV005220721.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Aug 14, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Achondrogenesis, type IB	Baylor Genetics Accession: SCV004201756.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Feb 15, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Atelosteogenesis type II Multiple epiphyseal dysplasia type 4 Achondrogenesis, type IB Diastrophic dysplasia Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005863350.2 First in ClinVar: Mar 04, 2025 Last updated: Feb 23, 2026	Publications: PubMed (5) PubMed: 11448940‚ 15294877‚ 21077204‚ 21922596‚ 8571951 Comment: show This sequence change creates a premature translational stop signal (p.Leu275Serfs*67) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 465 amino acid(s) of the SLC26A2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2678883). This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Ala715Val) have been determined to be pathogenic (PMID: 8571951, 11448940, 15294877, 21077204, 21922596; internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change creates a premature translational stop signal (p.Leu275Serfs*67) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 465 amino acid(s) of the SLC26A2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2678883). This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Ala715Val) have been determined to be pathogenic (PMID: 8571951, 11448940, 15294877, 21077204, 21922596; internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Pseudoachondroplasia and multiple epiphyseal dysplasia: a 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution.	Jackson GC	Human mutation	2012	PMID: 21922596
New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene.	Czarny-Ratajczak M	American journal of medical genetics. Part A	2010	PMID: 21077204
Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.	Karniski LP	Human molecular genetics	2004	PMID: 15294877
Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.	Karniski LP	Human molecular genetics	2001	PMID: 11448940
Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.	Hästbacka J	American journal of human genetics	1996	PMID: 8571951

Text-mined citations for rs2480774313 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 06, 2026