11-72577496-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_002599.5(PDE2A):c.2714G>T(p.Arg905Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R905C) has been classified as Uncertain significance.
Frequency
Consequence
NM_002599.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDE2A | NM_002599.5 | c.2714G>T | p.Arg905Leu | missense_variant | 31/31 | ENST00000334456.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDE2A | ENST00000334456.10 | c.2714G>T | p.Arg905Leu | missense_variant | 31/31 | 1 | NM_002599.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250834Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135610
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461370Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726982
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1965653). This variant has not been reported in the literature in individuals affected with PDE2A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 905 of the PDE2A protein (p.Arg905Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at