17-2778873-T-C

Position:

• chr17-2778873-T-C

Variant summary

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

The NM_001411048.1(RAP1GAP2):​c.167+8428T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,076 control chromosomes in the GnomAD database, including 12,368 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 0.40 (12368 hom., cov: 33)
• Consequence: RAP1GAP2 NM_001411048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.91

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GAP2	NM_001330058.2	c.-14+1926T>C		intron_variant			NP_001316987.1
RAP1GAP2	NM_001411048.1	c.167+8428T>C		intron_variant			NP_001397977.1
RAP1GAP2	XM_011523739.3	c.167+8428T>C		intron_variant			XP_011522041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000540393.6	c.-14+1595T>C		intron_variant		5		ENSP00000439688	A1
RAP1GAP2	ENST00000637138.1	c.167+8428T>C		intron_variant		5		ENSP00000490321

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60201 AN: 151958 Hom.: 12348 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.396 AC: 60251 AN: 152076 Hom.: 12368 Cov.: 33 AF XY: 0.391 AC XY: 29098 AN XY: 74340

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.367

Alfa AF: 0.350 Hom.: 12579

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12936006; hg19: chr17-2682167;