NM_006005.3(WFS1):c.2224dup (p.Cys742fs) AND Wolfram syndrome 1

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jun 5, 2019
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:: RCV000995912.5

Allele description [Variation Report for NM_006005.3(WFS1):c.2224dup (p.Cys742fs)]

NM_006005.3(WFS1):c.2224dup (p.Cys742fs)

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.2224dup (p.Cys742fs)

HGVS:

NC_000004.12:g.6302019dup
NG_011700.1:g.37170dup
NM_001145853.1:c.2224dup
NM_006005.3:c.2224dupMANE SELECT
NP_001139325.1:p.Cys742fs
NP_005996.2:p.Cys742fs
LRG_1417t1:c.2224dup
LRG_1417:g.37170dup
LRG_1417p1:p.Cys742fs
NC_000004.11:g.6303746dup

Protein change:

C742fs

Links:

dbSNP: rs1578612324

NCBI 1000 Genomes Browser:

rs1578612324

Molecular consequence:

NM_001145853.1:c.2224dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006005.3:c.2224dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Wolfram syndrome 1 (WFS1)
Identifiers:: MONDO: MONDO:0009101; MedGen: C4551693; Orphanet: 3463; OMIM: 222300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001150309	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Jun 5, 2019)	germline	clinical testing	Citation Link,
SCV003802940	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Likely pathogenic	unknown	research	PubMed (6) [See all records that cite these PMIDs] 20738327, 33879153, 12955714, 18060660, 20301750, 17603484 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001150309

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

criteria provided, single submitter

(Classification criteria August 2017)

Pathogenic
(Jun 5, 2019)

germline

clinical testing

Citation Link,

SCV003802940

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

criteria provided, single submitter

(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)

Likely pathogenic

unknown

research

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Wolfram syndrome and WFS1 gene.

Rigoli L, Lombardo F, Di Bella C.

Clin Genet. 2011 Feb;79(2):103-17. doi: 10.1111/j.1399-0004.2010.01522.x. Epub 2010 Aug 26. Review.

PubMed [citation]

PMID:: 20738327

A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1.

Gong Y, Xiong L, Li X, Su L, Xiao H.

BMC Endocr Disord. 2021 Apr 21;21(1):76. doi: 10.1186/s12902-021-00748-z.

PubMed [citation]

PMID:: 33879153
PMCID:: PMC8059287

See all PubMed Citations (6)

Details of each submission

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001150309.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	1	blood	not provided		1	not provided	not provided	not provided

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV003802940.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	research	PubMed (6)

Description

Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs1578612324 in Wolfram's syndrome yet.

#	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: Apr 20, 2024

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