9-21994197-G-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_058195.4(CDKN2A):āc.135C>Gā(p.Leu45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,606,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L45L) has been classified as Likely benign.
Frequency
Consequence
NM_058195.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.135C>G | p.Leu45= | synonymous_variant | 1/3 | ENST00000579755.2 | |
CDKN2A | NM_001363763.2 | c.-4+624C>G | intron_variant | ||||
CDKN2A | XM_047422597.1 | c.-4+350C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.135C>G | p.Leu45= | synonymous_variant | 1/3 | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000850 AC: 2AN: 235156Hom.: 0 AF XY: 0.00000768 AC XY: 1AN XY: 130130
GnomAD4 exome AF: 0.00000619 AC: 9AN: 1454200Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 723780
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152320Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74468
ClinVar
Submissions by phenotype
CDKN2A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2015 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at