17-2838482-G-C

Variant names:

• chr17-2838482-G-C
• rs9915696
• NM_015085.5:c.80+37932G>C

Variant summary

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

The NM_015085.5(RAP1GAP2):​c.80+37932G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,030 control chromosomes in the GnomAD database, including 2,661 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 0.18 (2661 hom., cov: 31)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	NM_015085.5	MANE Select	c.80+37932G>C		intron	N/A	NP_055900.4
	RAP1GAP2	NM_001411048.1		c.203+37932G>C		intron	N/A	NP_001397977.1
	RAP1GAP2	NM_001438816.1		c.203+37932G>C		intron	N/A	NP_001425745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000254695.13	TSL:1 MANE Select	c.80+37932G>C		intron	N/A	ENSP00000254695.8
	RAP1GAP2	ENST00000366401.8	TSL:1	c.80+37932G>C		intron	N/A	ENSP00000389824.2
	RAP1GAP2	ENST00000637138.1	TSL:5	c.203+37932G>C		intron	N/A	ENSP00000490321.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27758 AN: 151910 Hom.: 2658 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.183 AC: 27801 AN: 152030 Hom.: 2661 Cov.: 31 AF XY: 0.179 AC XY: 13327 AN XY: 74300

African (AFR) AF: 0.210 AC: 8712 AN: 41440

American (AMR) AF: 0.166 AC: 2528 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3468

East Asian (EAS) AF: 0.183 AC: 945 AN: 5162

South Asian (SAS) AF: 0.0799 AC: 385 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10606

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12464 AN: 67972

Other (OTH) AF: 0.199 AC: 419 AN: 2108

Alfa AF: 0.189 Hom.: 363

Bravo AF: 0.189

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.67
PhyloP100		-0.76
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: rs9915696; hg19: chr17-2741776;