NM_007194.4(CHEK2):c.1513T>A (p.Ser505Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Aug 4, 2021
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:: RCV000160441.15

Allele description [Variation Report for NM_007194.4(CHEK2):c.1513T>A (p.Ser505Thr)]

NM_007194.4(CHEK2):c.1513T>A (p.Ser505Thr)

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.1513T>A (p.Ser505Thr)

Other names:

p.S505T:TCC>ACC

HGVS:

NC_000022.11:g.28689164A>T
NG_008150.2:g.57703T>A
NM_001005735.2:c.1642T>A
NM_001257387.2:c.850T>A
NM_001349956.2:c.1312T>A
NM_007194.4:c.1513T>AMANE SELECT
NM_145862.2:c.1426T>A
NP_001005735.1:p.Ser548Thr
NP_001244316.1:p.Ser284Thr
NP_001336885.1:p.Ser438Thr
NP_009125.1:p.Ser505Thr
NP_665861.1:p.Ser476Thr
LRG_302t1:c.1513T>A
LRG_302:g.57703T>A
LRG_302p1:p.Ser505Thr
NC_000022.10:g.29085152A>T
NG_008150.1:g.57671T>A
NM_007194.3:c.1513T>A
p.S505T

Protein change:

S284T

Links:

dbSNP: rs587781960

NCBI 1000 Genomes Browser:

rs587781960

Molecular consequence:

NM_001005735.2:c.1642T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.850T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.1312T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.1513T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.1426T>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
SCV000215797	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (May 18, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25186627, 30287823, 30851065 Citation Link,
SCV000684606	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Oct 27, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002537388	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Aug 4, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000215797

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(May 18, 2021)

germline

clinical testing

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

Citation Link,

SCV000684606

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Oct 27, 2020)

germline

clinical testing

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

SCV002537388

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Aug 4, 2021)

germline

curation

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

Citations

PubMed

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000215797.7

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000684606.4

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

From Sema4, Sema4, SCV002537388.1

#	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

Last Updated: Sep 29, 2024

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