NM_000553.6(WRN):c.3382A>C (p.Ser1128Arg) AND Werner syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 9, 2023
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:: RCV000705250.5

Allele description [Variation Report for NM_000553.6(WRN):c.3382A>C (p.Ser1128Arg)]

NM_000553.6(WRN):c.3382A>C (p.Ser1128Arg)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

8p12

Genomic location:

Preferred name:

NM_000553.6(WRN):c.3382A>C (p.Ser1128Arg)

HGVS:

NC_000008.11:g.31143622A>C
NG_008870.1:g.115361A>C
NM_000553.6:c.3382A>CMANE SELECT
NP_000544.2:p.Ser1128Arg
LRG_524t1:c.3382A>C
LRG_524:g.115361A>C
NC_000008.10:g.31001138A>C
NM_000553.4:c.3382A>C

Protein change:

S1128R

Links:

dbSNP: rs1169330916

NCBI 1000 Genomes Browser:

rs1169330916

Molecular consequence:

NM_000553.6:c.3382A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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
SCV000834239	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32041611, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834239

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 9, 2023)

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

Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.

Dron JS, Wang J, McIntyre AD, Iacocca MA, Robinson JF, Ban MR, Cao H, Hegele RA.

BMC Med Genomics. 2020 Feb 10;13(1):23. doi: 10.1186/s12920-020-0669-2.

PubMed [citation]

PMID:: 32041611
PMCID:: PMC7011550

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, SCV000834239.5

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

Description

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1128 of the WRN protein (p.Ser1128Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with dyslipidemia (PMID: 32041611). ClinVar contains an entry for this variant (Variation ID: 581431). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine