Variant chr17-2980313-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015085.5(RAP1GAP2):c.623G>A(p.Arg208Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00179 in 1,613,822 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 15 hom. )

Consequence

RAP1GAP2
NM_015085.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.59

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009512484).

BP6

Variant 17-2980313-G-A is Benign according to our data. Variant chr17-2980313-G-A is described in ClinVar as [Benign]. Clinvar id is 768819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0092 (1400/152170) while in subpopulation AFR AF= 0.0317 (1317/41516). AF 95% confidence interval is 0.0303. There are 25 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5 link	c.623G>A	p.Arg208Gln	missense_variant	9/25	ENST00000254695.13	NP_055900.4	Q684P5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13 link	c.623G>A	p.Arg208Gln	missense_variant	9/25	1	NM_015085.5	ENSP00000254695.8		Q684P5-1

Frequencies

GnomAD3 genomes

AF:

0.00918

AC:

1396

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00246

AC:

612

AN:

249264

Hom.:

AF XY:

0.00182

AC XY:

246

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0331

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00101

AC:

1483

AN:

1461652

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

635

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00920

AC:

1400

AN:

152170

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

640

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.0110

ESP6500AA

AF:

0.0288

AC:

115

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00281

AC:

340

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.;T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;.;D;D

MetaRNN

Benign

0.0095

T;T;T;T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.3

.;.;M;.;M

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.95

.;N;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

0.37

.;T;T;T;T

Sift4G

Uncertain

0.056

.;T;T;T;T

Polyphen

0.98, 0.99

.;.;D;D;D

Vest4

0.35, 0.36, 0.35, 0.37

MVP

0.49

MPC

0.74

ClinPred

0.031

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.83

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over