Variant 13-97464207-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021033.7(RAP2A):c.317A>G(p.Tyr106Cys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

RAP2A
NM_021033.7 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94

Variant links:

Genes affected

RAP2A (HGNC:9861): (RAP2A, member of RAS oncogene family) Enables GTPase activity; guanyl ribonucleotide binding activity; and magnesium ion binding activity. Involved in several processes, including actin cytoskeleton reorganization; microvillus assembly; and positive regulation of protein autophosphorylation. Acts upstream of or within establishment of protein localization. Located in plasma membrane and recycling endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAP2A links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
RAP2A	NM_021033.7 linkuse as main transcript	c.317A>G	p.Tyr106Cys	missense_variant, splice_region_variant	2/2	ENST00000245304.5	NP_066361.1	P10114

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAP2A	ENST00000245304.5 linkuse as main transcript	c.317A>G	p.Tyr106Cys	missense_variant, splice_region_variant	2/2	1	NM_021033.7	ENSP00000245304.3	P10114
RAP2A	ENST00000476869.1 linkuse as main transcript	n.*73A>G		splice_region_variant, non_coding_transcript_exon_variant	3/3	3		ENSP00000436462.1	F6U784
RAP2A	ENST00000476869.1 linkuse as main transcript	n.*73A>G		3_prime_UTR_variant	3/3	3		ENSP00000436462.1	F6U784

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250566

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.317A>G (p.Y106C) alteration is located in exon 2 (coding exon 2) of the RAP2A gene. This alteration results from a A to G substitution at nucleotide position 317, causing the tyrosine (Y) at amino acid position 106 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.00069

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.080

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.57

MutationAssessor

Benign

-0.54

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.37

Sift

Benign

0.16

Sift4G

Benign

0.12

Polyphen

0.77

Vest4

0.66

MutPred

0.37

Loss of solvent accessibility (P = 0.0155);

MVP

0.53

MPC

2.9

ClinPred

0.81

GERP RS

5.8

Varity_R

0.66

gMVP

0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over