NM_006005.3(WFS1):c.1525_1539del (p.Val509_Tyr513del) AND Wolfram syndrome 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 22, 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:: RCV002274237.8

Allele description [Variation Report for NM_006005.3(WFS1):c.1525_1539del (p.Val509_Tyr513del)]

NM_006005.3(WFS1):c.1525_1539del (p.Val509_Tyr513del)

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.1525_1539del (p.Val509_Tyr513del)

Other names:

NG_011700.1:g.36471_36485del; NP_005996.2:p.(Val509_Tyr513del)

HGVS:

NC_000004.12:g.6301320_6301334del
NG_011700.1:g.36471_36485del
NM_001145853.1:c.1525_1539del
NM_006005.3:c.1525_1539delMANE SELECT
NP_001139325.1:p.Val509_Tyr513del
NP_005996.2:p.Val509_Tyr513del
LRG_1417t1:c.1525_1539del
LRG_1417:g.36471_36485del
LRG_1417p1:p.Val509_Tyr513del
NC_000004.11:g.6303037_6303051del
NC_000004.11:g.6303047_6303061del

Links:

OMIM: 606201.0002; dbSNP: rs781262017

NCBI 1000 Genomes Browser:

rs781262017

Molecular consequence:

NM_001145853.1:c.1525_1539del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_006005.3:c.1525_1539del - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

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

Recent activity

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Immunoglobulin lambda-Chains
Immunoglobulin lambda-Chains
One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.<br/>Year introduced: 2006 (1973)

MeSH
Leukemia, Plasma Cell
Leukemia, Plasma Cell
A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multipl...<br/>Year introduced: 2008 (1967)

MeSH
cytochrome b, partial (mitochondrion) [Plasmodium relictum]
cytochrome b, partial (mitochondrion) [Plasmodium relictum]
gi|1439540896|gb|AXI69776.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024942	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 1998)	germline	literature only	Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nature Genet. 20: 143-148, 1998.,
SCV004025923	Department Of Endocrinology, Sanjay Gandhi Postgraduate Institute Of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 15, 2023)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 28432734, 35602877, 32350710, 23373429, 33980734, 25741868
SCV005374459	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000024942

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 1998)

germline

literature only

Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nature Genet. 20: 143-148, 1998.,

SCV004025923

Department Of Endocrinology, Sanjay Gandhi Postgraduate Institute Of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 15, 2023)

unknown

clinical testing

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

SCV005374459

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 22, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Indian	unknown	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

Astuti D, Sabir A, Fulton P, Zatyka M, Williams D, Hardy C, Milan G, Favaretto F, Yu-Wai-Man P, Rohayem J, López de Heredia M, Hershey T, Tranebjaerg L, Chen JH, Chaussenot A, Nunes V, Marshall B, McAfferty S, Tillmann V, Maffei P, Paquis-Flucklinger V, Geberhiwot T, et al.

Hum Mutat. 2017 Jul;38(7):764-777. doi: 10.1002/humu.23233. Epub 2017 Jun 1.

PubMed [citation]

PMID:: 28432734
PMCID:: PMC5535005

Two Cases of Wolfram Syndrome Who Were Initially Diagnosed With Type 1 Diabetes.

Silvestri F, Tromba V, Costantino F, Palaniappan N, Urano F.

AACE Clin Case Rep. 2022 May-Jun;8(3):128-130. doi: 10.1016/j.aace.2022.01.001.

PubMed [citation]

PMID:: 35602877
PMCID:: PMC9123558

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000024942.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

In a consanguineous Japanese family segregating Wolfram syndrome (WFS1; 222300), Inoue et al. (1998) demonstrated that 4 affected sibs were homozygous for a 15-bp deletion in the WFS1 gene resulting in deletion of 5 amino acids, tyr-val-tyr-leu-leu, beginning with residue 508.

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

From Department Of Endocrinology, Sanjay Gandhi Postgraduate Institute Of Medical Sciences, SCV004025923.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Indian	1	not provided	not provided	clinical testing	PubMed (6)
2	Indian	1	not provided	not provided	clinical testing	PubMed (6)

Description

Proband presented with young onset, insulin requiring diabetes mellitus and was suspected to have type 1 diabetes mellitus. Underwent genetic testing since islet antibodies were negative.

Proband presented with young onset, insulin requiring diabetes mellitus and was suspected to have type 1 diabetes mellitus. Genetic testing done since all islet antibodies were negative.

Description

Homozygous 15 base pair deletion in exon 8 of the WFS1 gene (chr4:g.6301320_6301334del) that results in the in-frame deletion of 5 amino acids. The observed variation has previously been reported in patients affected with Wolfram syndrome. This variant has not been reported in the 1000 genomes and gnomAD databases. The reference region is conserved across species. PS1, PM1, PM2, PM4, PP3.

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV005374459.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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