NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 17, 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:: RCV003330882.1

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn)]

NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn)

Genes:

LOC123956210:Sharpr-MPRA regulatory region 3291 [Gene]
SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn)

HGVS:

NC_000007.14:g.107710134G>A
NG_008489.1:g.54500G>A
NM_000441.2:c.2170G>AMANE SELECT
NP_000432.1:p.Asp724Asn
NC_000007.13:g.107350579G>A
NM_000441.1:c.2170G>A

Protein change:

D724N

Links:

dbSNP: rs994170964

NCBI 1000 Genomes Browser:

rs994170964

Molecular consequence:

NM_000441.2:c.2170G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004037946	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004037946

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 17, 2023)

germline

clinical testing

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

Citation Link

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

Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.

Blons H, Feldmann D, Duval V, Messaz O, Denoyelle F, Loundon N, Sergout-Allaoui A, Houang M, Duriez F, Lacombe D, Delobel B, Leman J, Catros H, Journel H, Drouin-Garraud V, Obstoy MF, Toutain A, Oden S, Toublanc JE, Couderc R, Petit C, Garabédian EN, et al.

Clin Genet. 2004 Oct;66(4):333-40.

PubMed [citation]

PMID:: 15355436

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004037946.1

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

Description

Variant summary: SLC26A4 c.2170G>A (p.Asp724Asn) results in a conservative amino acid change located in the STAS domain (IPR002645) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 150994 control chromosomes (gnomAD). c.2170G>A has been reported in the literature as a biallelic genotype in at least one individual affected with Pendred Syndrome (Blons_2004). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, a different missense variant occuring at the same codon has been previously classified as pathogenic/likely pathogenic (p.Asp724Gly, ClinVar: 228396), suggesting this residue may be of clinical significance. The following publication has been ascertained in the context of this evaluation (PMID: 15355436). One ClinVar submitter has assessed the variant since 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly 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

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