NM_000112.4(SLC26A2):c.1926del (p.Leu644fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 16, 2021
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:: RCV001855612.4

Allele description [Variation Report for NM_000112.4(SLC26A2):c.1926del (p.Leu644fs)]

NM_000112.4(SLC26A2):c.1926del (p.Leu644fs)

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.1926del (p.Leu644fs)

HGVS:

NC_000005.10:g.149981519del
NG_007147.2:g.22637del
NM_000112.4:c.1926delMANE SELECT
NP_000103.2:p.Leu644fs
LRG_684:g.22637del
NC_000005.9:g.149361082del
NM_000112.3:c.1926delT

Protein change:

L644fs

Links:

dbSNP: rs1481910744

NCBI 1000 Genomes Browser:

rs1481910744

Molecular consequence:

NM_000112.4:c.1926del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Achondrogenesis, type IB (ACG1B)
Synonyms:: Achondrogenesis Fraccaro type
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; Atelosteogenesis type 2
Identifiers:: MONDO: MONDO:0009727; MedGen: C1850554; Orphanet: 56304; OMIM: 256050

Name:: Multiple epiphyseal dysplasia type 4 (EDM4)
Synonyms:: Multiple epiphyseal dysplasia, autosomal recessive; Multiple epiphyseal dysplasia with clubfoot; Multiple epiphyseal dysplasia with double-layered patella; 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236491	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 16, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11448940, 15294877, 21077204, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236491

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 16, 2021)

germline

clinical testing

PubMed (4)
[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

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

Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells.

Karniski LP.

Hum Mol Genet. 2004 Oct 1;13(19):2165-71. Epub 2004 Aug 4.

PubMed [citation]

PMID:: 15294877

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236491.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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: 11448940, 15294877, 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: 558379). This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu644Trpfs*6) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 96 amino acid(s) of the SLC26A2 protein.

#	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: Sep 29, 2024

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