17-2838482-G-C

Position:

• chr17-2838482-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1GAP2	NM_015085.5	c.80+37932G>C		intron_variant		ENST00000254695.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.80+37932G>C		intron_variant		1	NM_015085.5	P4
RAP1GAP2	ENST00000366401.8	c.80+37932G>C		intron_variant		1
RAP1GAP2	ENST00000540393.6	c.23+37932G>C		intron_variant		5		A1
RAP1GAP2	ENST00000637138.1	c.203+37932G>C		intron_variant		5

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

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0799

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.199

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.67

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: rs9915696; hg19: chr17-2741776; COSMIC: COSV54584837;