chr17-3002804-C-T

Variant names:

• chr17-3002804-C-T
• rs6502671
• NM_015085.5:c.1201-2565C>T

Variant summary

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

The NM_015085.5(RAP1GAP2):​c.1201-2565C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,162 control chromosomes in the GnomAD database, including 1,964 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 0.15 (1964 hom., cov: 32)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.1201-2565C>T		intron_variant	Intron 14 of 24	ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.1201-2565C>T		intron_variant	Intron 14 of 24	1	NM_015085.5	ENSP00000254695.8

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22723 AN: 152042 Hom.: 1963 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.149 AC: 22731 AN: 152162 Hom.: 1964 Cov.: 32 AF XY: 0.148 AC XY: 11011 AN XY: 74398

African (AFR) AF: 0.0673 AC: 2796 AN: 41520

American (AMR) AF: 0.171 AC: 2613 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5182

South Asian (SAS) AF: 0.117 AC: 565 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1395 AN: 10594

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12981 AN: 67968

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.180 Hom.: 7397

Bravo AF: 0.150

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.62
PhyloP100		-0.15
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: rs6502671; hg19: chr17-2906098;