NM_006005.3(WFS1):c.605A>G (p.Glu202Gly) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 21, 2023
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:: RCV000486801.8

Allele description

NM_006005.3(WFS1):c.605A>G (p.Glu202Gly)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.1

Genomic location:

Preferred name:

NM_006005.3(WFS1):c.605A>G (p.Glu202Gly)

HGVS:

NC_000004.12:g.6291341A>G
NG_011700.1:g.26492A>G
NM_001145853.1:c.605A>G
NM_006005.3:c.605A>GMANE SELECT
NP_001139325.1:p.Glu202Gly
NP_005996.2:p.Glu202Gly
LRG_1417t1:c.605A>G
LRG_1417:g.26492A>G
LRG_1417p1:p.Glu202Gly
NC_000004.11:g.6293068A>G

Protein change:

E202G

Links:

dbSNP: rs1064794257

NCBI 1000 Genomes Browser:

rs1064794257

Molecular consequence:

NM_001145853.1:c.605A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006005.3:c.605A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000568515	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 31, 2023)	germline	clinical testing	Citation Link,
SCV002234780	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 21, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23981289, 24117146, 28432734, 32179840, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568515

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 31, 2023)

germline

clinical testing

Citation Link,

SCV002234780

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 21, 2023)

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

Citations

PubMed

Phenotypic characteristics of early Wolfram syndrome.

Marshall BA, Permutt MA, Paciorkowski AR, Hoekel J, Karzon R, Wasson J, Viehover A, White NH, Shimony JS, Manwaring L, Austin P, Hullar TE, Hershey T; Washington University Wolfram Study Group..

Orphanet J Rare Dis. 2013 Apr 27;8:64. doi: 10.1186/1750-1172-8-64.

PubMed [citation]

PMID:: 23981289
PMCID:: PMC3651298

Novel homozygous mutation in exon 5 of WFS1 gene in an Apulian family with mild phenotypic expression of Wolfram syndrome.

Piccinno E, Ortolani F, Vendemiale M, Tummolo A, Masciopinto M, Natale MP, De Luca A, Agolini E, Aloi C, Salina A, D'Annunzio G, Fischetto R, Papadia F.

Clin Genet. 2014 Aug;86(2):197-8. doi: 10.1111/cge.12260. Epub 2013 Oct 3. No abstract available.

PubMed [citation]

PMID:: 24117146

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000568515.8

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29517769, 24117146, 28432734, 32179840, Mishra2021[Review], 23981289, 34970515, 26025012, 36227502, 35452662)

#	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		not provided	not provided	not provided	not provided

From Invitae, SCV002234780.3

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 202 of the WFS1 protein (p.Glu202Gly). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 23981289, 24117146, 28432734, 32179840; external communication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 420050). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WFS1 protein function. 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 16, 2024

ClinVar

Relating variation to medicine