chrX-132214254-G-T

Variant names:

• chrX-132214254-G-T
• rs371502735
• NM_001271186.2:c.466C>A

Variant summary

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

The NM_001271186.2(RAP2C):​c.466C>A​(p.Leu156Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,093 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
• Consequence: RAP2C NM_001271186.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63

Genes affected

RAP2C (HGNC:21165): (RAP2C, member of RAS oncogene family) The protein encoded by this gene is a member of the Ras-related protein subfamily of the Ras GTPase superfamily. Members of this family are small GTPases that act as molecular switches to regulate cellular proliferation, differentiation, and apoptosis. This protein has been reported to activate in vitro transcriptional activity of the serum response element. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

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
RAP2C	NM_001271186.2	c.466C>A	p.Leu156Ile	missense_variant	Exon 5 of 6	ENST00000370874.2	NP_001258115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP2C	ENST00000370874.2	c.466C>A	p.Leu156Ile	missense_variant	Exon 5 of 6	2	NM_001271186.2	ENSP00000359911.1
RAP2C	ENST00000342983.6	c.466C>A	p.Leu156Ile	missense_variant	Exon 3 of 4	1		ENSP00000340274.2
RAP2C	ENST00000620646.4	c.268C>A	p.Leu90Ile	missense_variant	Exon 5 of 6	5		ENSP00000484870.1
RAP2C	ENST00000460462.1	n.545C>A		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112093 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34263

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112093 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34263

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Benign	0.82
DEOGEN2	Benign	0.23	.;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.12	.;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.13	.;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.83	.;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0020	.;B;B
Vest4		0.61
MutPred		0.50		.;Loss of stability (P = 0.146);Loss of stability (P = 0.146);
MVP		0.86
MPC		1.3
ClinPred		0.79	D
GERP RS		5.6
Varity_R		0.38
gMVP		0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs371502735; hg19: chrX-131348282; COSMIC: COSV100747270; COSMIC: COSV100747270;