U.S. flag

An official website of the United States government

NM_007194.4(CHEK2):c.319+1G>A AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 23, 2019
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:
RCV001258068.2

Allele description [Variation Report for NM_007194.4(CHEK2):c.319+1G>A]

NM_007194.4(CHEK2):c.319+1G>A

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.319+1G>A
HGVS:
  • NC_000022.11:g.28734402C>T
  • NG_008150.2:g.12465G>A
  • NM_001005735.2:c.319+1G>A
  • NM_001257387.2:c.-459+1G>A
  • NM_001349956.2:c.319+1G>A
  • NM_007194.4:c.319+1G>AMANE SELECT
  • NM_145862.2:c.319+1G>A
  • LRG_302t1:c.319+1G>A
  • LRG_302:g.12465G>A
  • NC_000022.10:g.29130390C>T
  • NM_001005735.1:c.319+1G>A
  • NM_007194.3:c.319+1G>A
Links:
dbSNP: rs765080766
NCBI 1000 Genomes Browser:
rs765080766
Molecular consequence:
  • NM_001005735.2:c.319+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001257387.2:c.-459+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001349956.2:c.319+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007194.4:c.319+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_145862.2:c.319+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Breast cancer, susceptibility to
Identifiers:
MedGen: C3469522
Name:
RECLASSIFIED - CDH1 POLYMORPHISM
Synonyms:
Prostate cancer, susceptibility to
Identifiers:
MedGen: CN300425

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001434900Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 23, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001434900.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The c.319+1G>A variant occurs in the donor splice site of intron 2 of the CHEK2 gene and is predicted to affect splicing, likely resulting in disrupted or absent protein product via nonsense mediated decay. While this particular variant has not been reported in individuals with CHEK2-related cancer, a different variant also at the same donor splice site (c.319+2T>A) is associated with thyroid cancer, breast cancer, and colorectal cancer (PMID: 28608266, 26681312, 27696107). The c.319+1G>A variant is very rare in population databases (2/250812 alleles in gnomAD). Loss-of-function variants in CHEK2 are considered pathogenic (PMID: 21876083, 24713400). This variant has been classified as Likely Pathogenic, however due to low allele fraction detected on NGS in this sample, this could represent somatic mosaicism. The clinical significance of this finding warrants further investigation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024