3-141487097-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006506.5(RASA2):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000724 in 1,381,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RASA2
NM_006506.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276

Variant links:

Genes affected

RASA2 (HGNC:9872): (RAS p21 protein activator 2) The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

RASA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14472157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5 link	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 24	ENST00000286364.9	NP_006497.2	Q15283-2
RASA2	NM_001303246.3 link	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 25		NP_001290175.1	Q15283
RASA2	NM_001303245.3 link	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 24		NP_001290174.1	Q15283-1
RASA2	XM_047448652.1 link	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 17		XP_047304608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASA2	ENST00000286364.9 link	c.14C>T	p.Ala5Val	missense_variant	Exon 1 of 24	1	NM_006506.5	ENSP00000286364.3		Q15283-2
RASA2	ENST00000515549.1 link	n.14C>T		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000424293.1		D6RBA9

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000331

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

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

69962

Hom.:

AF XY:

0.00

AC XY:

AN XY:

39580

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000959

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

AF:

0.00000406

AC:

AN:

1230648

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

605214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000232

Gnomad4 NFE exome

AF:

0.00000203

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150438

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

73418

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000331

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:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.A5V variant (also known as c.14C>T), located in coding exon 1 of the RASA2 gene, results from a C to T substitution at nucleotide position 14. The alanine at codon 5 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.50

T;T

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.0

N;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.42

T;T

Vest4

0.16

MutPred

0.30

Gain of catalytic residue at A5 (P = 0.0093);Gain of catalytic residue at A5 (P = 0.0093);

MVP

0.73

MPC

0.34

ClinPred

0.64

GERP RS

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

gMVP

0.36

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