11-64728885-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

platelet-type bleeding disorder 18
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
osteopetrosis
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

RASGRP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.155

AC:

38279

AN:

247532

AF XY:

0.149

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 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

African (AFR)

AF:

0.110

AC:

3679

AN:

33470

American (AMR)

AF:

0.299

AC:

13342

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3771

AN:

26112

East Asian (EAS)

AF:

0.370

AC:

14672

AN:

39670

South Asian (SAS)

AF:

0.160

AC:

13805

AN:

86218

European-Finnish (FIN)

AF:

0.111

AC:

5787

AN:

51970

Middle Eastern (MID)

AF:

0.108

AC:

615

AN:

5706

European-Non Finnish (NFE)

AF:

0.0933

AC:

103663

AN:

1111408

Other (OTH)

AF:

0.123

AC:

7437

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7798

15596

23394

31192

38990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4098

8196

12294

16392

20490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19809

AN:

152228

Hom.:

1636

Cov.:

AF XY:

0.136

AC XY:

10123

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.111

AC:

4607

AN:

41558

American (AMR)

AF:

0.248

AC:

3786

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3468

East Asian (EAS)

AF:

0.348

AC:

1800

AN:

5166

South Asian (SAS)

AF:

0.170

AC:

821

AN:

4820

European-Finnish (FIN)

AF:

0.111

AC:

1174

AN:

10600

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0992

AC:

6745

AN:

68012

Other (OTH)

AF:

0.140

AC:

297

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

861

1723

2584

3446

4307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

3498

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

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

(source)

DANN

Benign

0.67

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over