17-2778873-T-C

Variant names:

• chr17-2778873-T-C
• rs12936006
• NM_001411048.1:c.167+8428T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411048.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	NM_001411048.1		c.167+8428T>C		intron	N/A	NP_001397977.1
	RAP1GAP2	NM_001438816.1		c.167+8428T>C		intron	N/A	NP_001425745.1
	RAP1GAP2	NM_001330058.2		c.-14+1926T>C		intron	N/A	NP_001316987.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000637138.1	TSL:5	c.167+8428T>C		intron	N/A	ENSP00000490321.1
	RAP1GAP2	ENST00000540393.6	TSL:5	c.-14+1595T>C		intron	N/A	ENSP00000439688.2

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

African (AFR) AF: 0.474 AC: 19669 AN: 41478

American (AMR) AF: 0.329 AC: 5027 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3275 AN: 5162

South Asian (SAS) AF: 0.369 AC: 1784 AN: 4832

European-Finnish (FIN) AF: 0.328 AC: 3478 AN: 10596

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24353 AN: 67952

Other (OTH) AF: 0.367 AC: 775 AN: 2114

Alfa AF: 0.367 Hom.: 36722

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.40
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12936006; hg19: chr17-2682167;