17-3030379-A-T

Variant names:

• chr17-3030379-A-T
• rs7216028
• NM_015085.5:c.2108-543A>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.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
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	NM_015085.5	MANE Select	c.2108-543A>T		intron	N/A	NP_055900.4
	RAP1GAP2	NM_001411048.1		c.2231-543A>T		intron	N/A	NP_001397977.1	A0A1B0GV05
	RAP1GAP2	NM_001438816.1		c.2186-543A>T		intron	N/A	NP_001425745.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000254695.13	TSL:1 MANE Select	c.2108-543A>T		intron	N/A	ENSP00000254695.8	Q684P5-1
	RAP1GAP2	ENST00000366401.8	TSL:1	c.2063-543A>T		intron	N/A	ENSP00000389824.2	Q684P5-2
	RAP1GAP2	ENST00000637138.1	TSL:5	c.2231-543A>T		intron	N/A	ENSP00000490321.1	A0A1B0GV05

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

African (AFR) AF: 0.110 AC: 4560 AN: 41474

American (AMR) AF: 0.178 AC: 2723 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.0932 AC: 483 AN: 5184

South Asian (SAS) AF: 0.132 AC: 639 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10574

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11888 AN: 67994

Other (OTH) AF: 0.178 AC: 375 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		0.0050
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: rs7216028; hg19: chr17-2933673;