rs6502656

Variant names:

• chr17-2977997-A-G
• rs6502656
• NM_015085.5:c.597-2290A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015085.5(RAP1GAP2):​c.597-2290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,932 control chromosomes in the GnomAD database, including 9,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9423 hom., cov: 31)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	NM_015085.5	MANE Select	c.597-2290A>G		intron	N/A	NP_055900.4
	RAP1GAP2	NM_001411048.1		c.720-2290A>G		intron	N/A	NP_001397977.1	A0A1B0GV05
	RAP1GAP2	NM_001438816.1		c.675-2290A>G		intron	N/A	NP_001425745.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000254695.13	TSL:1 MANE Select	c.597-2290A>G		intron	N/A	ENSP00000254695.8	Q684P5-1
	RAP1GAP2	ENST00000366401.8	TSL:1	c.552-2290A>G		intron	N/A	ENSP00000389824.2	Q684P5-2
	RAP1GAP2	ENST00000637138.1	TSL:5	c.720-2290A>G		intron	N/A	ENSP00000490321.1	A0A1B0GV05

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52883 AN: 151814 Hom.: 9407 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52916 AN: 151932 Hom.: 9423 Cov.: 31 AF XY: 0.347 AC XY: 25779 AN XY: 74234

African (AFR) AF: 0.276 AC: 11453 AN: 41436

American (AMR) AF: 0.355 AC: 5422 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2027 AN: 5154

South Asian (SAS) AF: 0.259 AC: 1251 AN: 4826

European-Finnish (FIN) AF: 0.429 AC: 4510 AN: 10512

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26053 AN: 67954

Other (OTH) AF: 0.328 AC: 693 AN: 2114

Alfa AF: 0.367 Hom.: 41645

Bravo AF: 0.340

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.28
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6502656; hg19: chr17-2881291;