rs4822983
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_007194.4(CHEK2):c.683+317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,804 control chromosomes in the GnomAD database, including 8,587 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.33 ( 8587 hom., cov: 31)
Consequence
CHEK2
NM_007194.4 intron
NM_007194.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.273
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHEK2 | NM_007194.4 | c.683+317G>A | intron_variant | ENST00000404276.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHEK2 | ENST00000404276.6 | c.683+317G>A | intron_variant | 1 | NM_007194.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.326 AC: 49403AN: 151686Hom.: 8575 Cov.: 31
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31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.326 AC: 49451AN: 151804Hom.: 8587 Cov.: 31 AF XY: 0.321 AC XY: 23770AN XY: 74160
GnomAD4 genome
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31
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23770
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74160
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595
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at