Variant 5-81070506-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000265080.9(RASGRF2):c.558T>A(p.Asn186Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,453,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RASGRF2
ENST00000265080.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

RASGRF2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08926442).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3 linkuse as main transcript	c.558T>A	p.Asn186Lys	missense_variant	4/27	ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9 linkuse as main transcript	c.558T>A	p.Asn186Lys	missense_variant	4/27	1	NM_006909.3	ENSP00000265080	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453360

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000453

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

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

Nov 09, 2023

The c.558T>A (p.N186K) alteration is located in exon 1 (coding exon 1) of the RASGRF2 gene. This alteration results from a T to A substitution at nucleotide position 558, causing the asparagine (N) at amino acid position 186 to be replaced by a lysine (K). 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.14

N;.

REVEL

Benign

0.070

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.036

B;.

Vest4

0.32

MutPred

0.28

Gain of solvent accessibility (P = 0.0086);Gain of solvent accessibility (P = 0.0086);

MVP

0.15

MPC

1.8

ClinPred

0.62

GERP RS

3.3

Varity_R

0.19

gMVP

0.65

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