rs2236141

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000416671.5(CHEK2):n.-120G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 602,986 control chromosomes in the GnomAD database, including 7,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1178 hom., cov: 31)

Exomes 𝑓: 0.15 ( 6116 hom. )

Consequence

CHEK2
ENST00000416671.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

CHEK2 (HGNC:16627): (checkpoint kinase 2) In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHEK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 22-28741882-C-T is Benign according to our data. Variant chr22-28741882-C-T is described in ClinVar as [Benign]. Clinvar id is 1167537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
CHEK2	NM_145862.2 link	c.-120G>A	upstream_gene_variant	NP_665861.1	O96017-12
CHEK2	XM_047441104.1 link	c.-120G>A	upstream_gene_variant	XP_047297060.1
CHEK2	XM_047441105.1 link	c.-120G>A	upstream_gene_variant	XP_047297061.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CHEK2	ENST00000416671.5 link	n.-120G>A	non_coding_transcript_exon_variant	Exon 1 of 16	1	ENSP00000402225.1	C9JFD7
CHEK2	ENST00000416671.5 link	n.-120G>A	5_prime_UTR_variant	Exon 1 of 16	1	ENSP00000402225.1	C9JFD7
CHEK2	ENST00000382580.6 link	c.-120G>A	upstream_gene_variant		1	ENSP00000372023.2	O96017-9
CHEK2	ENST00000348295.7 link	c.-120G>A	upstream_gene_variant		5	ENSP00000329012.5	O96017-12

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16260

AN:

152086

Hom.:

1181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.0914

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.137

GnomAD4 exome

AF:

0.152

AC:

68467

AN:

450782

Hom.:

6116

Cov.:

AF XY:

0.159

AC XY:

37737

AN XY:

236742

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0813

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.107

AC:

16258

AN:

152204

Hom.:

1178

Cov.:

AF XY:

0.108

AC XY:

8005

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.0842

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.118

Hom.:

175

Bravo

AF:

0.0997

Asia WGS

AF:

0.247

AC:

860

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20462940) -

Familial cancer of breast

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over