NM_000441.2(SLC26A4):c.916dup (p.Val306fs) AND Autosomal recessive nonsyndromic hearing loss 4

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 16, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001089561.4

Allele description [Variation Report for NM_000441.2(SLC26A4):c.916dup (p.Val306fs)]

NM_000441.2(SLC26A4):c.916dup (p.Val306fs)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.916dup (p.Val306fs)

HGVS:

NC_000007.14:g.107683352dup
NG_008489.1:g.27718dup
NM_000441.2:c.916dupMANE SELECT
NP_000432.1:p.Val306fs
NC_000007.13:g.107323796_107323797insG
NC_000007.13:g.107323797dup
NM_000441.1:c.916dupG
NM_000441.2:c.916dupGMANE SELECT

Protein change:

V306fs

Links:

dbSNP: rs768245266

NCBI 1000 Genomes Browser:

rs768245266

Molecular consequence:

NM_000441.2:c.916dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 4 (DFNB4)
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 4; DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC; Nonsyndromic enlarged vestibular aqueduct (NSEVA); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010933; MedGen: C3538946; Orphanet: 90636; OMIM: 600791

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001244770	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 27, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004201806	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 16, 2024)	unknown	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

SCV001244770

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 27, 2017)

unknown

clinical testing

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

SCV004201806

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 16, 2024)

unknown

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001244770.1

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

Description

A heterozygous duplication variant, NM_000441.1(SLC26A4):c.916dupG, has been identified in exon 7 of 21 of the SLC26A4 gene. This variant is predicted to cause a frameshift from amino acid position 306 and introduce a stop codon 24 residues downstream, NP_000432.1(SLC26A4):p.(Val306Glyfs*24), resulting in loss of protein function either through truncation (involving half of the protein including functional domains) or nonsense-mediated decay.This variant is present in the gnomAD database with a global frequency of 0.0014% (2 in 277028, 0 homozygotes) and in East Asian populations at a frequency of 0.02% (4 in 18862, 0 homozygotes). The variant has been previously described as pathogenic in multiple families withsevere to profoundhearing loss(ClinVar, Li, Q. et al. (2012), Lee, HJ. et al. (2014),Mori, K.et al. (2016), Wang, Q-J. et al. (2007),Jung, J. et al. (2017)). Based on current informationthis variant has been classified as PATHOGENIC.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004201806.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	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