rs541513166

Variant names:

• chr22-28687820-TA-T
• rs541513166
• NM_007194.4:c.*76delT

Your query was ambiguous. Multiple possible variants found:

• chr22-28687820-TA-T
• chr22-28687820-TA-TAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_007194.4(CHEK2):​c.*76delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHEK2 NM_007194.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK2	NM_007194.4	c.*76delT		3_prime_UTR_variant	Exon 15 of 15	ENST00000404276.6	NP_009125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHEK2	ENST00000404276	c.*76delT		3_prime_UTR_variant	Exon 15 of 15	1	NM_007194.4	ENSP00000385747.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 240 AN: 143536 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000905

Gnomad EAS AF: 0.00143

Gnomad SAS AF: 0.00408

Gnomad FIN AF: 0.00392

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.00363

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000108 AC: 11 AN: 1018114 Hom.: 0 Cov.: 13 AF XY: 0.0000134 AC XY: 7 AN XY: 521942

Gnomad4 AFR exome AF: 0.0000400

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000868

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000952

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00167 AC: 240 AN: 143654 Hom.: 0 Cov.: 32 AF XY: 0.00203 AC XY: 142 AN XY: 69848

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000905

Gnomad4 EAS AF: 0.00144

Gnomad4 SAS AF: 0.00408

Gnomad4 FIN AF: 0.00392

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.00359

Alfa AF: 0.000273 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs541513166; hg19: chr22-29083808;