rs201656017

Variant names:

• chr17-2981247-A-C
• NM_015085.5:c.728A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-2981247-A-C
• chr17-2981247-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015085.5(RAP1GAP2):​c.728A>C​(p.Lys243Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000206 in 1,457,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K243R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RAP1GAP2 NM_015085.5 missense, splice_region
• Scores: Splicing: ADA: 0.5706
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.728A>C	p.Lys243Thr	missense_variant, splice_region_variant	Exon 10 of 25	ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.728A>C	p.Lys243Thr	missense_variant, splice_region_variant	Exon 10 of 25	1	NM_015085.5	ENSP00000254695.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457572 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;.;D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Uncertain	2.7	.;.;M;.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.7	.;D;D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0080	.;D;D;D;D
Sift4G	Uncertain	0.012	.;D;D;D;D
Polyphen		1.0	.;.;D;D;D
Vest4		0.49, 0.50, 0.51, 0.49
MutPred		0.32		.;.;Loss of ubiquitination at K243 (P = 0.0116);.;Loss of ubiquitination at K243 (P = 0.0116);
MVP		0.89
MPC		1.4
ClinPred		0.99	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.35
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.57
dbscSNV1_RF	Benign	0.61
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-2884541;