NM_000112.4(SLC26A2):c.1630del (p.Leu544fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 2022
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:: RCV002886471.4

Allele description [Variation Report for NM_000112.4(SLC26A2):c.1630del (p.Leu544fs)]

NM_000112.4(SLC26A2):c.1630del (p.Leu544fs)

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.1630del (p.Leu544fs)

HGVS:

NC_000005.10:g.149981223del
NG_007147.2:g.22341del
NM_000112.4:c.1630delMANE SELECT
NP_000103.2:p.Leu544Serfs
NP_000103.2:p.Leu544fs
LRG_684t1:c.1630del
LRG_684:g.22341del
LRG_684p1:p.Leu544Serfs
NC_000005.9:g.149360785del
NC_000005.9:g.149360786del
NM_000112.3:c.1630delC

Protein change:

L544fs

Links:

dbSNP: rs2480776557

NCBI 1000 Genomes Browser:

rs2480776557

Molecular consequence:

NM_000112.4:c.1630del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003247030	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 8, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21077204, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003247030

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 8, 2022)

germline

clinical testing

PubMed (2)
[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

New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene.

Czarny-Ratajczak M, Bieganski T, Rogala P, Glowacki M, Trzeciak T, Kozlowski K.

Am J Med Genet A. 2010 Dec;152A(12):3036-42. doi: 10.1002/ajmg.a.33707.

PubMed [citation]

PMID:: 21077204

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003247030.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SLC26A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu544Serfs*41) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 196 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: May 16, 2025

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