rs543243963

Variant names:

• chr17-2905313-C-A
• rs543243963
• NM_015085.5:c.110C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-2905313-C-A
• chr17-2905313-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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]

ACMG classification

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
RAP1GAP2	NM_015085.5	c.110C>A	p.Ala37Glu	missense_variant	Exon 3 of 25	ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.110C>A	p.Ala37Glu	missense_variant	Exon 3 of 25	1	NM_015085.5	ENSP00000254695.8

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

Other links and lift over

dbSNP: rs543243963; hg19: chr17-2808607;