NM_007194.4(CHEK2):c.1331A>G (p.Lys444Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 3, 2022
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:: RCV002257882.4

Allele description [Variation Report for NM_007194.4(CHEK2):c.1331A>G (p.Lys444Arg)]

NM_007194.4(CHEK2):c.1331A>G (p.Lys444Arg)

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.1331A>G (p.Lys444Arg)

HGVS:

NC_000022.11:g.28695171T>C
NG_008150.2:g.51696A>G
NM_001005735.2:c.1460A>G
NM_001257387.2:c.668A>G
NM_001349956.2:c.1130A>G
NM_007194.4:c.1331A>GMANE SELECT
NM_145862.2:c.1244A>G
NP_001005735.1:p.Lys487Arg
NP_001244316.1:p.Lys223Arg
NP_001336885.1:p.Lys377Arg
NP_009125.1:p.Lys444Arg
NP_665861.1:p.Lys415Arg
LRG_302t1:c.1331A>G
LRG_302:g.51696A>G
LRG_302p1:p.Lys444Arg
NC_000022.10:g.29091159T>C
NG_008150.1:g.51664A>G
NM_007194.3:c.1331A>G

Protein change:

K223R

Links:

dbSNP: rs1555913454

NCBI 1000 Genomes Browser:

rs1555913454

Molecular consequence:

NM_001005735.2:c.1460A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.668A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.1130A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1331A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.1244A>G - 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
SCV002537046	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Nov 22, 2021)	germline	curation	Citation Link,
SCV002692592	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 3, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002537046

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Nov 22, 2021)

germline

curation

Citation Link,

SCV002692592

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 3, 2022)

germline

clinical testing

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, curation

Details of each submission

From Sema4, Sema4, SCV002537046.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	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 Ambry Genetics, SCV002692592.2

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

Description

The p.K444R variant (also known as c.1331A>G), located in coding exon 11 of the CHEK2 gene, results from an A to G substitution at nucleotide position 1331. The lysine at codon 444 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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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