NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jan 19, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001232144.4

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly)]

NM_000441.2(SLC26A4):c.2171A>G (p.Asp724Gly)

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.2171A>G (p.Asp724Gly)
HGVS:
  • NC_000007.14:g.107710135A>G
  • NG_008489.1:g.54501A>G
  • NM_000441.2:c.2171A>GMANE SELECT
  • NP_000432.1:p.Asp724Gly
  • NC_000007.13:g.107350580A>G
  • NM_000441.1:c.2171A>G
Protein change:
D724G
Links:
dbSNP: rs757820624
NCBI 1000 Genomes Browser:
rs757820624
Molecular consequence:
  • NM_000441.2:c.2171A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001404690Invitaecriteria provided, single submitter
Pathogenic
(Jun 9, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV001874181GeneDxcriteria provided, single submitter
Pathogenic
(Jan 19, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations.

Prasad S, Kölln KA, Cucci RA, Trembath RC, Van Camp G, Smith RJ.

Am J Med Genet A. 2004 Jan 1;124A(1):1-9.

PubMed [citation]
PMID:
14679580

Pendred's syndrome and non-syndromic DFNB4 deafness associated with the homozygous T410M mutation in the SLC26A4 gene in siblings.

Arellano B, Pera A, Ramírez-Camacho R, Villamar M, Trinidad A, García JR, Moreno F, Hernández-Chico C.

Clin Genet. 2005 May;67(5):438-40. No abstract available.

PubMed [citation]
PMID:
15811013
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001404690.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces aspartic acid with glycine at codon 724 of the SLC26A4 protein (p.Asp724Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs757820624, ExAC 0.02%). This variant has been observed in individual(s) with Pendred syndrome or nonsyndromic enlarged vestibular aqueduct (PMID: 14679580, 15811013, 24224479). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 228396). This variant has been reported to affect SLC26A4 protein function (PMID: 19017801). This variant disrupts the p.Asp724 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC26A4-related conditions (PMID: 15355436, 27344577), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001874181.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Published functional studies demonstrate a damaging effect on iodide transport (Pera et al., 2008); This variant is associated with the following publications: (PMID: 31589614, 24224479, 14679580, 19017801, 15811013, 24860705, 15355436, 19509082, 25491636, 18285825, 27344577, 20668687)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 23, 2021

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