NM_007194.4(CHEK2):c.164C>T (p.Ser55Phe) AND Familial cancer of breast

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 6, 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:: RCV000466798.13

Allele description [Variation Report for NM_007194.4(CHEK2):c.164C>T (p.Ser55Phe)]

NM_007194.4(CHEK2):c.164C>T (p.Ser55Phe)

Gene:

CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.164C>T (p.Ser55Phe)

HGVS:

NC_000022.11:g.28734558G>A
NG_008150.2:g.12309C>T
NM_001005735.2:c.164C>T
NM_001257387.2:c.-614C>T
NM_001349956.2:c.164C>T
NM_007194.4:c.164C>TMANE SELECT
NM_145862.2:c.164C>T
NP_001005735.1:p.Ser55Phe
NP_001336885.1:p.Ser55Phe
NP_009125.1:p.Ser55Phe
NP_665861.1:p.Ser55Phe
LRG_302t1:c.164C>T
LRG_302:g.12309C>T
LRG_302p1:p.Ser55Phe
NC_000022.10:g.29130546G>A
NG_008150.1:g.12277C>T
NM_007194.3:c.164C>T

Protein change:

S55F

Links:

dbSNP: rs765799649

NCBI 1000 Genomes Browser:

rs765799649

Molecular consequence:

NM_001257387.2:c.-614C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.164C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550562	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31871109, 22006311, 28492532
SCV005058358	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 6, 2024)	unknown	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

SCV000550562

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 18, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005058358

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 6, 2024)

unknown

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

Citations

PubMed

Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon.

Adedokun B, Zheng Y, Ndom P, Gakwaya A, Makumbi T, Zhou AY, Yoshimatsu TF, Rodriguez A, Madduri RK, Foster IT, Sallam A, Olopade OI, Huo D.

Cancer Epidemiol Biomarkers Prev. 2020 Feb;29(2):359-367. doi: 10.1158/1055-9965.EPI-19-0506. Epub 2019 Dec 23.

PubMed [citation]

PMID:: 31871109
PMCID:: PMC7007381

Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.

Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM.

Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18032-7. doi: 10.1073/pnas.1115052108. Epub 2011 Oct 17.

PubMed [citation]

PMID:: 22006311
PMCID:: PMC3207658

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550562.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 55 of the CHEK2 protein (p.Ser55Phe). This variant is present in population databases (rs765799649, gnomAD 0.01%). This missense change has been observed in individual(s) with ovarian, peritoneal or fallopian tube cancer (PMID: 22006311, 31871109). ClinVar contains an entry for this variant (Variation ID: 410069). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect CHEK2 function (PMID: 22006311). 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

From Baylor Genetics, SCV005058358.1

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

Last Updated: Sep 29, 2024

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