Variant chr17-2796562-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015085.5(RAP1GAP2):c.35G>A(p.Gly12Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAP1GAP2
NM_015085.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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]

RAP1GAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5 link	c.35G>A	p.Gly12Asp	missense_variant	1/25	ENST00000254695.13	NP_055900.4	Q684P5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAP1GAP2	ENST00000254695.13 link	c.35G>A	p.Gly12Asp	missense_variant	1/25	1	NM_015085.5	ENSP00000254695.8	Q684P5-1
RAP1GAP2	ENST00000366401.8 link	c.35G>A	p.Gly12Asp	missense_variant	1/24	1		ENSP00000389824.2	Q684P5-2
RAP1GAP2	ENST00000637138.1 link	c.168-3953G>A		intron_variant		5		ENSP00000490321.1	A0A1B0GV05
RAP1GAP2	ENST00000540393.6 link	c.-13-3953G>A		intron_variant		5		ENSP00000439688.2	Q684P5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696984

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.35G>A (p.G12D) alteration is located in exon 1 (coding exon 1) of the RAP1GAP2 gene. This alteration results from a G to A substitution at nucleotide position 35, causing the glycine (G) at amino acid position 12 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

.;T;T

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.54

N;N;N

REVEL

Uncertain

0.58

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.72

MutPred

0.38

Loss of MoRF binding (P = 0.0341);Loss of MoRF binding (P = 0.0341);Loss of MoRF binding (P = 0.0341);

MVP

0.78

MPC

0.79

ClinPred

0.89

GERP RS

4.8

Varity_R

0.25

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over