NM_007194.4(CHEK2):c.253C>A (p.Pro85Thr) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 20, 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:: RCV002037037.7

Allele description [Variation Report for NM_007194.4(CHEK2):c.253C>A (p.Pro85Thr)]

NM_007194.4(CHEK2):c.253C>A (p.Pro85Thr)

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.253C>A (p.Pro85Thr)

HGVS:

NC_000022.11:g.28734469G>T
NG_008150.2:g.12398C>A
NM_001005735.2:c.253C>A
NM_001257387.2:c.-525C>A
NM_001349956.2:c.253C>A
NM_007194.4:c.253C>AMANE SELECT
NM_145862.2:c.253C>A
NP_001005735.1:p.Pro85Thr
NP_001336885.1:p.Pro85Thr
NP_009125.1:p.Pro85Thr
NP_665861.1:p.Pro85Thr
LRG_302t1:c.253C>A
LRG_302:g.12398C>A
LRG_302p1:p.Pro85Thr
NC_000022.10:g.29130457G>T

Protein change:

P85T

Links:

dbSNP: rs1366081066

NCBI 1000 Genomes Browser:

rs1366081066

Molecular consequence:

NM_001257387.2:c.-525C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.253C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.253C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.253C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.253C>A - 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

Recent activity

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membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 iso...
membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 isoform X12 [Mus musculus]
gi|1720414155|ref|XP_030110517.1|

Protein
Waterborne Diseases
Waterborne Diseases
Illnesses due to micro-organisms and chemicals in drinking water, those caused by organisms having part of their lifecycle in water or those with water-related vectors, and ot...<br/>Year introduced: 2016

MeSH
PREDICTED: B-cell receptor-associated protein 31 [Tarenaya hassleriana]
PREDICTED: B-cell receptor-associated protein 31 [Tarenaya hassleriana]
gi|729376115|ref|XP_010549208.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318285	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 20, 2022)	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

SCV002318285

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 20, 2022)

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

Citations

PubMed

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, SCV002318285.3

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

Description

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 85 of the CHEK2 protein (p.Pro85Thr). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant is not present in population databases (gnomAD no frequency).

#	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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