rs12603284

chr17-2868218-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015085.5(RAP1GAP2):c.81-37066C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,066 control chromosomes in the GnomAD database, including 1,777 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 0.10 (1777 hom., cov: 32)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1GAP2	NM_015085.5	c.81-37066C>T		intron_variant		ENST00000254695.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.81-37066C>T		intron_variant		1	NM_015085.5	P4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15835 AN: 151948 Hom.: 1767 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.104 AC: 15862 AN: 152066 Hom.: 1777 Cov.: 32 AF XY: 0.114 AC XY: 8498 AN XY: 74308

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0928 Hom.: 2045

Bravo AF: 0.109

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.9
Dann	Benign	0.72

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: rs12603284; hg19: chr17-2771512;