Variant 11-64735891-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098671.2(RASGRP2):c.1173+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,609,534 control chromosomes in the GnomAD database, including 16,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2403 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13708 hom. )

Consequence

RASGRP2
NM_001098671.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.02

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-64735891-G-A is Benign according to our data. Variant chr11-64735891-G-A is described in ClinVar as [Benign]. Clinvar id is 403364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP2	NM_001098671.2 linkuse as main transcript	c.1173+12C>T		intron_variant		ENST00000394432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP2	ENST00000394432.8 linkuse as main transcript	c.1173+12C>T		intron_variant		1	NM_001098671.2	P4	Q7LDG7-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24237

AN:

151974

Hom.:

2391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0997

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.165

AC:

40850

AN:

247614

Hom.:

4575

AF XY:

0.157

AC XY:

21067

AN XY:

134126

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.303

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0948

Gnomad OTH exome

AF:

0.137

GnomAD4 exome

AF:

0.118

AC:

172357

AN:

1457442

Hom.:

13708

Cov.:

AF XY:

0.119

AC XY:

86139

AN XY:

725154

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.0932

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.160

AC:

24302

AN:

152092

Hom.:

2403

Cov.:

AF XY:

0.164

AC XY:

12219

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0997

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.110

Hom.:

1201

Bravo

AF:

0.175

Asia WGS

AF:

0.280

AC:

974

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

-0.88

CADD

Benign

1.5

DANN

Benign

0.50

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