NM_006005.3(WFS1):c.9dup (p.Asn4fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2024
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:: RCV001389688.7

Allele description [Variation Report for NM_006005.3(WFS1):c.9dup (p.Asn4fs)]

NM_006005.3(WFS1):c.9dup (p.Asn4fs)

Gene:

WFS1:wolframin ER transmembrane glycoprotein [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4p16.1

Genomic location:

Preferred name:

NM_006005.3(WFS1):c.9dup (p.Asn4fs)

HGVS:

NC_000004.12:g.6277464dup
NG_011700.1:g.12615dup
NM_001145853.1:c.9dup
NM_006005.3:c.9dupMANE SELECT
NP_001139325.1:p.Asn4fs
NP_005996.2:p.Asn4fs
LRG_1417t1:c.9dup
LRG_1417:g.12615dup
LRG_1417p1:p.Asn4fs
NC_000004.11:g.6279189_6279190insC
NC_000004.11:g.6279191dup

Protein change:

N4fs

Links:

dbSNP: rs2109107823

NCBI 1000 Genomes Browser:

rs2109107823

Molecular consequence:

NM_001145853.1:c.9dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006005.3:c.9dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591138	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 1, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12955714, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591138

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 1, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.

Cryns K, Sivakumaran TA, Van den Ouweland JM, Pennings RJ, Cremers CW, Flothmann K, Young TL, Smith RJ, Lesperance MM, Van Camp G.

Hum Mutat. 2003 Oct;22(4):275-87. Review.

PubMed [citation]

PMID:: 12955714

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591138.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Asn4Glnfs*52) in the WFS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WFS1 are known to be pathogenic (PMID: 12955714). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1075961). For these reasons, this variant has been 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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