Variant 5-80960771-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006909.3(RASGRF2):c.33C>G(p.His11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,322 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000055 ( 1 hom. )

Consequence

RASGRF2
NM_006909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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:

RASGRF2-AS1 (HGNC:40499): (RASGRF2 antisense RNA 1)

RASGRF2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.302092).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RASGRF2	NM_006909.3 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/27	ENST00000265080.9
RASGRF2-AS1	NR_105015.1 linkuse as main transcript	n.127+10G>C		intron_variant, non_coding_transcript_variant
RASGRF2	XM_005248565.2 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/19
RASGRF2	XM_017009683.2 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RASGRF2	ENST00000265080.9 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/27	1	NM_006909.3	P1
RASGRF2	ENST00000503795.1 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant, NMD_transcript_variant	1/28	1
RASGRF2-AS1	ENST00000505694.1 linkuse as main transcript	n.127+10G>C		intron_variant, non_coding_transcript_variant		3
RASGRF2	ENST00000638442.1 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242444

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456322

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723808

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:

0.0000934

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Feb 11, 2022

The c.33C>G (p.H11Q) alteration is located in exon 1 (coding exon 1) of the RASGRF2 gene. This alteration results from a C to G substitution at nucleotide position 33, causing the histidine (H) at amino acid position 11 to be replaced by a glutamine (Q). 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

0.85

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.69

N;.

REVEL

Benign

0.28

Sift

Benign

0.34

T;.

Sift4G

Benign

0.72

T;.

Polyphen

0.13

B;.

Vest4

0.47

MutPred

0.46

Gain of MoRF binding (P = 0.079);Gain of MoRF binding (P = 0.079);

MVP

0.50

MPC

2.0

ClinPred

0.64

GERP RS

3.4

Varity_R

0.23

gMVP

0.59

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