Variant 11-64729045-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001098671.2(RASGRP2):c.1592-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,591,750 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 82 hom. )

Consequence

RASGRP2
NM_001098671.2 splice_region, intron

Scores

Splicing: ADA: 0.9562

Clinical Significance

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

Conservation

PhyloP100: 2.18

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:

RASGRP2 (HGNC:):

RASGRP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 11-64729045-G-T is Benign according to our data. Variant chr11-64729045-G-T is described in ClinVar as [Benign]. Clinvar id is 284960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRP2	NM_001098671.2 linkuse as main transcript	c.1592-3C>A		splice_region_variant, intron_variant		ENST00000394432.8	NP_001092141.1	Q7LDG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRP2	ENST00000394432.8 linkuse as main transcript	c.1592-3C>A		splice_region_variant, intron_variant		1	NM_001098671.2	ENSP00000377953.3		Q7LDG7-1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2738

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0601

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00576

AC:

1260

AN:

218840

Hom.:

AF XY:

0.00442

AC XY:

526

AN XY:

119112

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.00383

Gnomad ASJ exome

AF:

0.00819

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00214

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.00373

GnomAD4 exome

AF:

0.00262

AC:

3766

AN:

1439446

Hom.:

Cov.:

AF XY:

0.00245

AC XY:

1755

AN XY:

715430

show subpopulations

Gnomad4 AFR exome

AF:

0.0619

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00859

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00243

Gnomad4 FIN exome

AF:

0.0000245

Gnomad4 NFE exome

AF:

0.000691

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.0180

AC:

2742

AN:

152304

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1282

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0600

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00818

Hom.:

Bravo

AF:

0.0203

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 25, 2015	- -
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 -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	This variant is associated with the following publications: (PMID: 27884173, 17576779, 25525159) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.96

dbscSNV1_RF

Pathogenic

0.85

SpliceAI score (max)

0.010

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