NM_006005.3(WFS1):c.1243_1245del (p.Val415del) AND WFS1-Related Spectrum Disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 5, 2022
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:: RCV001849340.6

Allele description [Variation Report for NM_006005.3(WFS1):c.1243_1245del (p.Val415del)]

NM_006005.3(WFS1):c.1243_1245del (p.Val415del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4p16.1

Genomic location:

Preferred name:

NM_006005.3(WFS1):c.1243_1245del (p.Val415del)

Other names:

WFS1, 3-BP DEL, VAL415DEL

HGVS:

NC_000004.11:g.6302763_6302765del
NC_000004.12:g.6301038_6301040del
NG_011700.1:g.36189_36191del
NM_001145853.1:c.1243_1245del
NM_006005.3:c.1243_1245delMANE SELECT
NP_001139325.1:p.Val415del
NP_005996.2:p.Val415del
LRG_1417t1:c.1243_1245del
LRG_1417:g.36189_36191del
LRG_1417p1:p.Val415del
NC_000004.11:g.6302763_6302765del
NC_000004.11:g.6302765_6302767del
NC_000004.11:g.6302765_6302767delGTC
NM_006005.3:c.1243_1245del
NM_006005.3:c.1243_1245delGTCMANE SELECT
p.V415del

Protein change:

V415del; VAL415DEL

Links:

OMIM: 606201.0029; dbSNP: rs863224265

NCBI 1000 Genomes Browser:

rs863224265

Molecular consequence:

NM_001145853.1:c.1243_1245del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_006005.3:c.1243_1245del - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Name:: WFS1-Related Spectrum Disorders
Identifiers:: MedGen: CN239410

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002107143	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21538838, 27617222, 23429432, 19042979, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002107143

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 5, 2022)

germline

clinical testing

PubMed (5)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.

Rendtorff ND, Lodahl M, Boulahbel H, Johansen IR, Pandya A, Welch KO, Norris VW, Arnos KS, Bitner-Glindzicz M, Emery SB, Mets MB, Fagerheim T, Eriksson K, Hansen L, Bruhn H, Möller C, Lindholm S, Ensgaard S, Lesperance MM, Tranebjaerg L.

Am J Med Genet A. 2011 Jun;155A(6):1298-313. doi: 10.1002/ajmg.a.33970. Epub 2011 Apr 28.

PubMed [citation]

PMID:: 21538838
PMCID:: PMC3100366

Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome.

Bodoor K, Batiha O, Abu-Awad A, Al-Sarihin K, Ziad H, Jarun Y, Abu-Sheikha A, Abu Jalboush S, Alibrahim KS.

Meta Gene. 2016 Sep;9:219-24. doi: 10.1016/j.mgene.2016.07.003.

PubMed [citation]

PMID:: 27617222
PMCID:: PMC5006133

See all PubMed Citations (5)

Details of each submission

From DASA, SCV002107143.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 21538838) - PS3_supporting. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 215406; PMID: 27617222; PMID: 23429432; PMID: 19042979) - PS4. The variant is present at low allele frequencies population databases (rs863224265 – gnomAD 0.0008545%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Val415del) was detected in trans with a pathogenic variant (PMID: 27617222; PMID: 19042979) - PM3. Protein length variants as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants - PM4. The variant co-segregated with disease in multiple affected family members (PMID: 27617222) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic.

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

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine