NM_000112.4(SLC26A2):c.1064_1065insAAAAA (p.Asn355fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 24, 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:: RCV001947014.6

Allele description [Variation Report for NM_000112.4(SLC26A2):c.1064_1065insAAAAA (p.Asn355fs)]

NM_000112.4(SLC26A2):c.1064_1065insAAAAA (p.Asn355fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_000112.4(SLC26A2):c.1064_1065insAAAAA (p.Asn355fs)

HGVS:

NC_000005.10:g.149980657_149980658insAAAAA
NG_007147.2:g.21775_21776insAAAAA
NM_000112.4:c.1064_1065insAAAAAMANE SELECT
NP_000103.2:p.Asn355fs
LRG_684:g.21775_21776insAAAAA
NC_000005.9:g.149360216_149360217insAAAAA
NC_000005.9:g.149360220_149360221insAAAAA

Protein change:

N355fs

Links:

dbSNP: rs2113698201

NCBI 1000 Genomes Browser:

rs2113698201

Molecular consequence:

NM_000112.4:c.1064_1065insAAAAA - 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
SCV002241376	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 24, 2021)	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

SCV002241376

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 24, 2021)

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, SCV002241376.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SLC26A2 protein. Other variant(s) that disrupt this region (p.Glu703Glyfs*9) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals 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.Asn355Lysfs*26) in the SLC26A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 385 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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