rs59403466

Variant names:

• chr17-2882601-T-G
• rs59403466
• NM_015085.5:c.81-22683T>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.81-22683T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 152,244 control chromosomes in the GnomAD database, including 115 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 0.036 (115 hom., cov: 32)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.81-22683T>G		intron_variant	Intron 2 of 24	ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.81-22683T>G		intron_variant	Intron 2 of 24	1	NM_015085.5	ENSP00000254695.8

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5533 AN: 152126 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0363 AC: 5529 AN: 152244 Hom.: 115 Cov.: 32 AF XY: 0.0357 AC XY: 2661 AN XY: 74444

African (AFR) AF: 0.0674 AC: 2798 AN: 41532

American (AMR) AF: 0.0252 AC: 386 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0472 AC: 164 AN: 3472

East Asian (EAS) AF: 0.00676 AC: 35 AN: 5176

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4832

European-Finnish (FIN) AF: 0.0157 AC: 167 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1756 AN: 68012

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0299 Hom.: 17

Bravo AF: 0.0394

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.26
PhyloP100		0.56
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: rs59403466; hg19: chr17-2785895;