rs12603284

Variant names:

• chr17-2868218-C-T
• rs12603284
• NM_015085.5:c.81-37066C>T

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

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
• Publications: 9 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=-0.84).
• 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 rank	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.81-37066C>T		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.81-37066C>T		intron_variant	Intron 2 of 24	1	NM_015085.5	ENSP00000254695.8

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

African (AFR) AF: 0.0504 AC: 2092 AN: 41524

American (AMR) AF: 0.198 AC: 3022 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3028 AN: 5160

South Asian (SAS) AF: 0.178 AC: 855 AN: 4812

European-Finnish (FIN) AF: 0.189 AC: 1995 AN: 10546

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4381 AN: 67982

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.0932 Hom.: 3095

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
PhyloP100		-0.51
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: rs12603284; hg19: chr17-2771512;