rs543243963

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015085.5(RAP1GAP2):​c.110C>A​(p.Ala37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RAP1GAP2
NM_015085.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09
Variant links:
Genes affected
RAP1GAP2 (HGNC:29176): (RAP1 GTPase activating protein 2) This gene encodes a GTPase-activating protein that activates the small guanine-nucleotide-binding protein Rap1 in platelets. The protein interacts with synaptotagmin-like protein 1 and Rab27 and regulates secretion of dense granules from platelets at sites of endothelial damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10568938).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAP1GAP2NM_015085.5 linkc.110C>A p.Ala37Glu missense_variant Exon 3 of 25 ENST00000254695.13 NP_055900.4 Q684P5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAP1GAP2ENST00000254695.13 linkc.110C>A p.Ala37Glu missense_variant Exon 3 of 25 1 NM_015085.5 ENSP00000254695.8 Q684P5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.099
D
BayesDel_noAF
Benign
-0.090
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.017
T;.;T;.;T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.80
T;T;.;T;T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
0.34
.;.;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.30
.;N;N;N;N
REVEL
Benign
0.27
Sift
Uncertain
0.0040
.;D;D;D;D
Sift4G
Uncertain
0.010
.;D;D;T;D
Polyphen
0.033, 0.023
.;.;B;B;B
Vest4
0.46, 0.43, 0.48
MutPred
0.11
.;.;Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);Gain of solvent accessibility (P = 0.0023);
MVP
0.28
MPC
0.58
ClinPred
0.57
D
GERP RS
3.1
Varity_R
0.19
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs543243963; hg19: chr17-2808607; API