NM_007194.4(CHEK2):c.83C>A (p.Ser28Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 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:: RCV003368013.2

Allele description [Variation Report for NM_007194.4(CHEK2):c.83C>A (p.Ser28Tyr)]

NM_007194.4(CHEK2):c.83C>A (p.Ser28Tyr)

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.83C>A (p.Ser28Tyr)

HGVS:

NC_000022.11:g.28734639G>T
NG_008150.2:g.12228C>A
NM_001005735.2:c.83C>A
NM_001257387.2:c.-695C>A
NM_001349956.2:c.83C>A
NM_007194.3:c.83C>A
NM_007194.4:c.83C>AMANE SELECT
NM_145862.2:c.83C>A
NP_001005735.1:p.Ser28Tyr
NP_001336885.1:p.Ser28Tyr
NP_009125.1:p.Ser28Tyr
NP_665861.1:p.Ser28Tyr
LRG_302t1:c.83C>A
LRG_302:g.12228C>A
LRG_302p1:p.Ser28Tyr
NC_000022.10:g.29130627G>T

Protein change:

S28Y

Molecular consequence:

NM_001257387.2:c.-695C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.83C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.83C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.83C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.83C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004055680	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004055680

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 13, 2023)

germline

clinical testing

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

Citation Link

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

Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients.

Vargas-Parra G, Del Valle J, Rofes P, Gausachs M, Stradella A, Moreno-Cabrera JM, Velasco A, Tornero E, Menéndez M, Muñoz X, Iglesias S, López-Doriga A, Azuara D, Campos O, Cuesta R, Darder E, de Cid R, González S, Teulé A, Navarro M, Brunet J, Capellá G, et al.

Hum Mutat. 2020 Dec;41(12):2128-2142. doi: 10.1002/humu.24110. Epub 2020 Oct 14.

PubMed [citation]

PMID:: 32906215

Details of each submission

From Ambry Genetics, SCV004055680.2

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

Description

The p.S28Y variant (also known as c.83C>A), located in coding exon 1 of the CHEK2 gene, results from a C to A substitution at nucleotide position 83. The serine at codon 28 is replaced by tyrosine, an amino acid with dissimilar properties. One study reported this alteration in an individual undergoing testing for suspected hereditary cancer (Vargas-Parra G et al. Hum Mutat, 2020 Dec;41:2128-2142). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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