rs1554659242
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_058195.4(CDKN2A):āc.28C>Gā(p.Arg10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,616 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_058195.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.28C>G | p.Arg10Gly | missense_variant | 1/3 | ENST00000579755.2 | |
CDKN2A | NM_001363763.2 | c.-4+517C>G | intron_variant | ||||
CDKN2A | XM_047422597.1 | c.-4+243C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.28C>G | p.Arg10Gly | missense_variant | 1/3 | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1452616Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 721924
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The p.R10G variant (also known as c.28C>G), located in coding exon 1 of the CDKN2A (p14ARF) gene, results from a C to G substitution at nucleotide position 28. The arginine at codon 10 is replaced by glycine, an amino acid with dissimilar properties. This alteration was identified in a 69-year-old male patient with superficial spreading melanoma (Zaremba A et al. Eur J Cancer, 2019 Sep;119:66-76). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at