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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 30, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV005220721.1

Allele description [Variation Report for NM_000112.4(SLC26A2):c.822del (p.Leu275fs)]

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

Gene:

SLC26A2:solute carrier family 26 member 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

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

HGVS:

NC_000005.10:g.149980415del
NG_007147.2:g.21533del
NM_000112.4:c.822delMANE SELECT
NP_000103.2:p.Leu275Serfs
NP_000103.2:p.Leu275fs
LRG_684t1:c.822del
LRG_684:g.21533del
LRG_684p1:p.Leu275Serfs
NC_000005.9:g.149359976del
NC_000005.9:g.149359978del
NM_000112.3:c.822delG

Protein change:

L275fs

Links:

dbSNP: rs2480774313

NCBI 1000 Genomes Browser:

rs2480774313

Molecular consequence:

NM_000112.4:c.822del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Achondrogenesis, type IB (ACG1B)
Identifiers:: MONDO: MONDO:0010966; MedGen: C0265274; Orphanet: 932; Orphanet: 93298; OMIM: 600972

Name:: Atelosteogenesis type II (AO2)
Synonyms:: NEONATAL OSSEOUS DYSPLASIA I; Neonatal osseous dysplasia 1
Identifiers:: MONDO: MONDO:0009727; MedGen: C1850554; Orphanet: 56304; OMIM: 256050

Name:: Multiple epiphyseal dysplasia type 4 (EDM4)
Synonyms:: MULTIPLE EPIPHYSEAL DYSPLASIA WITH BILAYERED PATELLAE; MULTIPLE EPIPHYSEAL DYSPLASIA WITH CLUBFOOT; MULTIPLE EPIPHYSEAL DYSPLASIA, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009189; MedGen: C1847593; Orphanet: 93307; OMIM: 226900

Name:: Diastrophic dysplasia (DTD)
Synonyms:: Diastrophic dwarfism
Identifiers:: MONDO: MONDO:0009107; MedGen: C0220726; Orphanet: 628; OMIM: 222600

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005863350	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 8571951, 11448940, 15294877, 21077204, 21922596, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005863350

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES.

Am J Hum Genet. 1996 Feb;58(2):255-62.

PubMed [citation]

PMID:: 8571951
PMCID:: PMC1914552

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.

Karniski LP.

Hum Mol Genet. 2001 Jul 1;10(14):1485-90.

PubMed [citation]

PMID:: 11448940

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005863350.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine