NM_000553.6(WRN):c.648dup (p.Ala217fs) AND Werner syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 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:: RCV001224126.5

Allele description [Variation Report for NM_000553.6(WRN):c.648dup (p.Ala217fs)]

NM_000553.6(WRN):c.648dup (p.Ala217fs)

Gene:

WRN:WRN RecQ like helicase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

8p12

Genomic location:

Preferred name:

NM_000553.6(WRN):c.648dup (p.Ala217fs)

HGVS:

NC_000008.11:g.31067176dup
NG_008870.1:g.38915dup
NM_000553.6:c.648dupMANE SELECT
NP_000544.2:p.Ala217fs
LRG_524t1:c.648dup
LRG_524:g.38915dup
NC_000008.10:g.30924691_30924692insT
NC_000008.10:g.30924692dup
NM_000553.4:c.648dup

Protein change:

A217fs

Links:

dbSNP: rs1812741645

NCBI 1000 Genomes Browser:

rs1812741645

Molecular consequence:

NM_000553.6:c.648dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Werner syndrome (WRN)
Synonyms:: Werner's syndrome
Identifiers:: MONDO: MONDO:0010196; MedGen: C0043119; Orphanet: 902; OMIM: 277700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001396307	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16673358, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001396307

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2022)

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

The spectrum of WRN mutations in Werner syndrome patients.

Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, et al.

Hum Mutat. 2006 Jun;27(6):558-67.

PubMed [citation]

PMID:: 16673358
PMCID:: PMC1868417

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, SCV001396307.4

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 952082). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala217Cysfs*16) in the WRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358).

#	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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