X-132214200-C-A

Position:

• chrX-132214200-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271186.2(RAP2C):​c.520G>T​(p.Asp174Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RAP2C NM_001271186.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35685998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP2C	NM_001271186.2	c.520G>T	p.Asp174Tyr	missense_variant	5/6	ENST00000370874.2	NP_001258115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP2C	ENST00000370874.2	c.520G>T	p.Asp174Tyr	missense_variant	5/6	2	NM_001271186.2	ENSP00000359911	P1
RAP2C	ENST00000342983.6	c.520G>T	p.Asp174Tyr	missense_variant	3/4	1		ENSP00000340274	P1
RAP2C	ENST00000620646.4	c.322G>T	p.Asp108Tyr	missense_variant	5/6	5		ENSP00000484870
RAP2C	ENST00000460462.1	n.599G>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.520G>T (p.D174Y) alteration is located in exon 3 (coding exon 2) of the RAP2C gene. This alteration results from a G to T substitution at nucleotide position 520, causing the aspartic acid (D) at amino acid position 174 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.1	.;L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	.;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.017	.;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.68	.;P;P
Vest4		0.41
MutPred		0.38		.;Loss of disorder (P = 0.0343);Loss of disorder (P = 0.0343);
MVP		0.98
MPC		1.5
ClinPred		0.91	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-131348228;