rs11515
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000077.5(CDKN2A):c.*29G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,732 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 28)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CDKN2A
NM_000077.5 3_prime_UTR
NM_000077.5 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.62
Genes affected
CDKN2A (HGNC:1787): (cyclin dependent kinase inhibitor 2A) This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.*29G>T | 3_prime_UTR_variant | 3/3 | ENST00000304494.10 | ||
CDKN2A | NM_058195.4 | c.*144G>T | 3_prime_UTR_variant | 3/3 | ENST00000579755.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.*29G>T | 3_prime_UTR_variant | 3/3 | 1 | NM_000077.5 | P2 | ||
CDKN2A | ENST00000579755.2 | c.*144G>T | 3_prime_UTR_variant | 3/3 | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 genomes
?
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28
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251310Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135836
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458732Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 725958
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GnomAD4 genome ? Cov.: 28
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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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