Genetic Variant RASGRP2:p.Gly583Gly (chr11-64728885-G-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001098671.2(RASGRP2):c.1749C>A(p.Gly583Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,611,766 control chromosomes in the GnomAD database, including 13,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1636 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12315 hom. )

Consequence

RASGRP2
NM_001098671.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.770

Variant links:

Genes affected

RASGRP2 (HGNC:9879): (RAS guanyl releasing protein 2) The protein encoded by this gene is a brain-enriched nucleotide exchanged factor that contains an N-terminal GEF domain, 2 tandem repeats of EF-hand calcium-binding motifs, and a C-terminal diacylglycerol/phorbol ester-binding domain. This protein can activate small GTPases, including RAS and RAP1/RAS3. The nucleotide exchange activity of this protein can be stimulated by calcium and diacylglycerol. Four alternatively spliced transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

RASGRP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 11-64728885-G-T is Benign according to our data. Variant chr11-64728885-G-T is described in ClinVar as [Benign]. Clinvar id is 403363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP2	NM_001098671.2 link	c.1749C>A	p.Gly583Gly	synonymous_variant	Exon 15 of 17	ENST00000394432.8	NP_001092141.1	Q7LDG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP2	ENST00000394432.8 link	c.1749C>A	p.Gly583Gly	synonymous_variant	Exon 15 of 17	1	NM_001098671.2	ENSP00000377953.3		Q7LDG7-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19775

AN:

152110

Hom.:

1633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.155

AC:

38279

AN:

247532

Hom.:

3985

AF XY:

0.149

AC XY:

19980

AN XY:

134234

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.352

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0945

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.114

AC:

166771

AN:

1459538

Hom.:

12315

Cov.:

AF XY:

0.115

AC XY:

83582

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0933

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.130

AC:

19809

AN:

152228

Hom.:

1636

Cov.:

AF XY:

0.136

AC XY:

10123

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0992

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.112

Hom.:

1827

Bravo

AF:

0.141

Asia WGS

AF:

0.259

AC:

901

AN:

3478

EpiCase

AF:

0.0990

EpiControl

AF:

0.100

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.4

DANN

Benign

0.67

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