chr9-21971150-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000077.5(CDKN2A):c.209C>G(p.Pro70Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P70T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000077.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.209C>G | p.Pro70Arg | missense_variant | 2/3 | ENST00000304494.10 | |
CDKN2A | NM_058195.4 | c.252C>G | p.Ala84= | synonymous_variant | 2/3 | ENST00000579755.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.209C>G | p.Pro70Arg | missense_variant | 2/3 | 1 | NM_000077.5 | P2 | |
CDKN2A | ENST00000579755.2 | c.252C>G | p.Ala84= | synonymous_variant | 2/3 | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442188Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 717480
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2019 | The p.P70R variant (also known as c.209C>G), located in coding exon 2 of the CDKN2A gene, results from a C to G substitution at nucleotide position 209. The proline at codon 70 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in a familial melanoma kindred (Soufir N et al, Br. J. Cancer 2004 Jan; 90(2):503-9). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at