chr17-3030379-A-T

Position:

• chr17-3030379-A-T

Variant summary

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

The NM_015085.5(RAP1GAP2):​c.2108-543A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,096 control chromosomes in the GnomAD database, including 1,803 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 (1803 hom., cov: 32)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.2108-543A>T		intron_variant		ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.2108-543A>T		intron_variant		1	NM_015085.5	ENSP00000254695	P4

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22800 AN: 151978 Hom.: 1802 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.150 AC: 22813 AN: 152096 Hom.: 1803 Cov.: 32 AF XY: 0.148 AC XY: 11016 AN XY: 74376

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0932

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.178

Alfa AF: 0.0864 Hom.: 126

Bravo AF: 0.153

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.69

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: rs7216028; hg19: chr17-2933673;