chr17-2981229-A-T

Variant names:

• chr17-2981229-A-T
• rs367931879
• NM_015085.5:c.710A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015085.5(RAP1GAP2):​c.710A>T​(p.Asn237Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N237S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAP1GAP2 NM_015085.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.710A>T	p.Asn237Ile	missense	Exon 10 of 25	NP_055900.4
	RAP1GAP2	NM_001411048.1		c.833A>T	p.Asn278Ile	missense	Exon 11 of 26	NP_001397977.1	A0A1B0GV05
	RAP1GAP2	NM_001438816.1		c.788A>T	p.Asn263Ile	missense	Exon 10 of 25	NP_001425745.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000254695.13	TSL:1 MANE Select	c.710A>T	p.Asn237Ile	missense	Exon 10 of 25	ENSP00000254695.8	Q684P5-1
	RAP1GAP2	ENST00000366401.8	TSL:1	c.665A>T	p.Asn222Ile	missense	Exon 9 of 24	ENSP00000389824.2	Q684P5-2
	RAP1GAP2	ENST00000637138.1	TSL:5	c.833A>T	p.Asn278Ile	missense	Exon 11 of 26	ENSP00000490321.1	A0A1B0GV05

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460112 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726136

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111174

Other (OTH) AF: 0.0000166 AC: 1 AN: 60324

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Pathogenic	0.67
Sift	Benign	0.29	T
Sift4G	Benign	0.39	T
Polyphen		0.95	P
Vest4		0.52
MutPred		0.53		Gain of sheet (P = 0.0477)
MVP		0.73
MPC		0.63
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.72

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: rs367931879; hg19: chr17-2884523;