NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg) AND Pendred syndrome

Clinical significance:Likely benign (Last evaluated: Oct 2, 2019)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV001004774.4

Allele description [Variation Report for NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg)]

NM_000441.2(SLC26A4):c.147C>G (p.Ser49Arg)

Genes:
SLC26A4-AS1:SLC26A4 antisense RNA 1 [Gene - HGNC]
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.147C>G (p.Ser49Arg)
HGVS:
  • NC_000007.14:g.107661788C>G
  • NG_008489.1:g.6154C>G
  • NM_000441.2:c.147C>GMANE SELECT
  • NP_000432.1:p.Ser49Arg
  • NC_000007.13:g.107302233C>G
  • NM_000441.1:c.147C>G
  • NM_000441.2(SLC26A4):c.147C>GMANE SELECT
  • NR_028137.1:n.11G>C
Protein change:
S49R
Links:
dbSNP: rs756969021
NCBI 1000 Genomes Browser:
rs756969021
Molecular consequence:
  • NM_000441.2:c.147C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_028137.1:n.11G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
functionally_normal [Sequence Ontology: SO:0002219]
Observations:
1

Condition(s)

Name:
Pendred syndrome (PDS)
Synonyms:
HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2B; THYROID DYSHORMONOGENESIS 2B; THYROID HORMONOGENESIS, GENETIC DEFECT IN, 2B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010134; MedGen: C0271829; Orphanet: 705; OMIM: 274600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001164256ClinGen Hearing Loss Variant Curation Expert Panelreviewed by expert panel
Likely benign
(Oct 2, 2019)
germlinecuration

Citation Link,

SCV001326718Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001438731The Core Laboratory in Medical Center of Clinical Research,Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicineno assertion criteria providedBenign
(May 12, 2020)
inheritedclinical testing

SCV001455792Natera, Inc.no assertion criteria providedLikely benign
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedinheritedyes1not providednot provided1not providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling.

Li Q, Zhu QW, Yuan YY, Huang SS, Han DY, Huang DL, Dai P.

J Transl Med. 2012 Nov 14;10:225. doi: 10.1186/1479-5876-10-225.

PubMed [citation]
PMID:
23151025
PMCID:
PMC3514144

Molecular analysis of hearing loss associated with enlarged vestibular aqueduct in the mainland Chinese: a unique SLC26A4 mutation spectrum.

Hu H, Wu L, Feng Y, Pan Q, Long Z, Li J, Dai H, Xia K, Liang D, Niikawa N, Xia J.

J Hum Genet. 2007;52(6):492-497. doi: 10.1007/s10038-007-0139-0. Epub 2007 Apr 19.

PubMed [citation]
PMID:
17443271
See all PubMed Citations (3)

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV001164256.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The SLC26A4 p.Ser49Arg variant has been identified in a heterozygous state in two Chinese individuals with congenital non-syndromic hearing loss (PMID: 25149764). No information about segregation of the variant or whether it was in trans with another SLC26A4 variant was given. The filtering allele frequency of the p.Ser49Arg variant in the SLC26A4 gene is 0.27% for East Asian chromosomes by gnomAD (44/12282 with 95% CI), which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). Additionally, computational prediction analysis using the metapredictor tool REVEL suggests that the variant may not impact the protein (BP4). Splice prediction analysis using MaxEntScan does not suggest an impact to splicing (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : BS1_Supporting, BP4.

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

From Illumina Clinical Services Laboratory,Illumina, SCV001326718.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From The Core Laboratory in Medical Center of Clinical Research,Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, SCV001438731.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyes1not providednot provided1not providednot providednot provided

From Natera, Inc., SCV001455792.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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