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

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Apr 1, 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:: RCV000409855.7

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:: Pendred syndrome (PDS)
Synonyms:: DEAFNESS WITH GOITER; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2B; THYROID DYSHORMONOGENESIS 2B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010134; MedGen: C0271829; Orphanet: 705; OMIM: 274600

Recent activity

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Mus musculus PRKC, apoptosis, WT1, regulator (Pawr), mRNA
Mus musculus PRKC, apoptosis, WT1, regulator (Pawr), mRNA
gi|119392099|ref|NM_054056.2|

Nucleotide
Gene Links for GEO Profiles (Select 85800291) (1)
Gene
PF3D7_0320900 [Plasmodium falciparum 3D7]
PF3D7_0320900 [Plasmodium falciparum 3D7]
Gene ID:814523

Gene
PF3D7_0322900 [Plasmodium falciparum 3D7]
PF3D7_0322900 [Plasmodium falciparum 3D7]
Gene ID:814544

Gene
Gene Links for GEO Profiles (Select 85800351) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000485440	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Dec 11, 2015)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV002026721	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002079981	Natera, Inc.	no assertion criteria provided	Pathogenic (Dec 2, 2020)	germline	clinical testing
SCV005075995	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Apr 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China.

Wang QJ, Zhao YL, Rao SQ, Guo YF, Yuan H, Zong L, Guan J, Xu BC, Wang DY, Han MK, Lan L, Zhai SQ, Shen Y.

Clin Genet. 2007 Sep;72(3):245-54.

PubMed [citation]

PMID:: 17718863

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

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000485440.2

#	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

From Genome-Nilou Lab, SCV002026721.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002079981.1

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

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005075995.1

#	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.916dupG (p.Val306GlyfsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251278 control chromosomes (gnomAD). c.916dupG has been reported in the literature in multiple individuals affected with non syndromic enlarged vestibular aqueduct (example: Chai_2013). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 23918157). ClinVar contains an entry for this variant (Variation ID: 370192). Based on the evidence outlined above, the variant was classified as 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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