Variant rs1033667 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007194.4(CHEK2):c.319+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,259,652 control chromosomes in the GnomAD database, including 50,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6926 hom., cov: 32)

Exomes 𝑓: 0.27 ( 43541 hom. )

Consequence

CHEK2
NM_007194.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.497

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 22-28734312-C-T is Benign according to our data. Variant chr22-28734312-C-T is described in ClinVar as [Benign]. Clinvar id is 1292603.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHEK2	NM_007194.4 linkuse as main transcript	c.319+91G>A		intron_variant		ENST00000404276.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHEK2	ENST00000404276.6 linkuse as main transcript	c.319+91G>A		intron_variant		1	NM_007194.4	P2	O96017-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44765

AN:

151910

Hom.:

6910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.275

AC:

304485

AN:

1107624

Hom.:

43541

AF XY:

0.270

AC XY:

151736

AN XY:

561960

show subpopulations

Gnomad4 AFR exome

AF:

0.345

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.295

AC:

44817

AN:

152028

Hom.:

6926

Cov.:

AF XY:

0.292

AC XY:

21681

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.275

Hom.:

5918

Bravo

AF:

0.304

Asia WGS

AF:

0.190

AC:

658

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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