9-21994240-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_058195.4(CDKN2A):āc.92C>Gā(p.Thr31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,605,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_058195.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.92C>G | p.Thr31Arg | missense_variant | Exon 1 of 3 | ENST00000579755.2 | NP_478102.2 | |
CDKN2A | NM_001363763.2 | c.-4+581C>G | intron_variant | Intron 1 of 2 | NP_001350692.1 | |||
CDKN2A | XM_047422597.1 | c.-4+307C>G | intron_variant | Intron 1 of 2 | XP_047278553.1 | |||
LOC124902130 | XR_007061436.1 | n.-212C>G | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151852Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000908 AC: 21AN: 231346Hom.: 0 AF XY: 0.0000936 AC XY: 12AN XY: 128180
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1453270Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 723108
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151972Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74270
ClinVar
Submissions by phenotype
Melanoma-pancreatic cancer syndrome Uncertain:2
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. -
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not specified Benign:1
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not provided Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Familial melanoma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at