NM_000112.4(SLC26A2):c.1537_1541dup (p.Ile514fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV001850977.4

Allele description [Variation Report for NM_000112.4(SLC26A2):c.1537_1541dup (p.Ile514fs)]

NM_000112.4(SLC26A2):c.1537_1541dup (p.Ile514fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_000112.4(SLC26A2):c.1537_1541dup (p.Ile514fs)

HGVS:

NC_000005.10:g.149981130_149981134dup
NG_007147.2:g.22248_22252dup
NM_000112.4:c.1537_1541dupMANE SELECT
NP_000103.2:p.Ile514fs
LRG_684:g.22248_22252dup
NC_000005.9:g.149360692_149360693insGTTAT
NC_000005.9:g.149360693_149360697dup

Protein change:

I514fs

Links:

dbSNP: rs1057517511

NCBI 1000 Genomes Browser:

rs1057517511

Molecular consequence:

NM_000112.4:c.1537_1541dup - 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

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
SCV002235510	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235510

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002235510.3

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

Description

This sequence change creates a premature translational stop signal (p.Ile514Metfs*14) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 226 amino acid(s) of the SLC26A2 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 371758). This variant disrupts a region of the SLC26A2 protein in which other variant(s) (p.Glu703Glyfs*9) have been determined to be pathogenic (Invitae). 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: Sep 29, 2024

ClinVar

Relating variation to medicine