rs200129494
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000077.5(CDKN2A):c.150+214del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,612,006 control chromosomes in the GnomAD database, including 44 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0096 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 23 hom. )
Consequence
CDKN2A
NM_000077.5 intron
NM_000077.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.338
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 Benign. Variant got -10 ACMG points.
BP6
?
Variant 9-21974463-AC-A is Benign according to our data. Variant chr9-21974463-AC-A is described in ClinVar as [Benign]. Clinvar id is 402524.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00962 (1466/152326) while in subpopulation AFR AF= 0.0321 (1336/41564). AF 95% confidence interval is 0.0307. There are 21 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1466 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.150+214del | intron_variant | ENST00000304494.10 | |||
CDKN2A | NM_058195.4 | c.194-3256del | intron_variant | ENST00000579755.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.150+214del | intron_variant | 1 | NM_000077.5 | P2 | |||
CDKN2A | ENST00000579755.2 | c.194-3256del | intron_variant | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00961 AC: 1463AN: 152208Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00115 AC: 288AN: 250770Hom.: 7 AF XY: 0.000781 AC XY: 106AN XY: 135682
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GnomAD4 exome AF: 0.00112 AC: 1640AN: 1459680Hom.: 23 Cov.: 31 AF XY: 0.000964 AC XY: 700AN XY: 726170
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GnomAD4 genome ? AF: 0.00962 AC: 1466AN: 152326Hom.: 21 Cov.: 32 AF XY: 0.00894 AC XY: 666AN XY: 74490
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
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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