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NM_007194.4(CHEK2):c.319+1G>T AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 1, 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:
RCV002325499.3

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

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

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

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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002609548Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 1, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002609548.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.319+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 1 of the CHEK2 gene. In silico splice site analysis predicts that this alteration will weaken the native splice donor site, which is predicted to result in the in frame deletion of CDS1. As such, this alteration may escape nonsense-mediated mRNAdecay and/or be prone to rescue by reinitiation; however, direct evidence is insufficient at this time (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Oct 20, 2024