Variant 22-39968118-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004810.4(GRAP2):c.536G>A(p.Arg179Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00899 in 1,608,518 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0092 ( 104 hom. )

Consequence

GRAP2
NM_004810.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

GRAP2 (HGNC:4563): (GRB2 related adaptor protein 2) This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

GRAP2 links:

GRAP2 (HGNC:):

GRAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049968064).

BP6

Variant 22-39968118-G-A is Benign according to our data. Variant chr22-39968118-G-A is described in ClinVar as [Benign]. Clinvar id is 708853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAP2	NM_004810.4 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	6/8	ENST00000344138.9	NP_004801.1	O75791-1Q6FI14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GRAP2	ENST00000344138.9 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	6/8	1	NM_004810.4	ENSP00000339186.4	O75791-1
GRAP2	ENST00000407075.3 linkuse as main transcript	c.536G>A	p.Arg179Gln	missense_variant	5/7	1		ENSP00000385607.3	O75791-1
GRAP2	ENST00000481263.1 linkuse as main transcript	n.186G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00671

AC:

1021

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00901

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00877

AC:

2076

AN:

236692

Hom.:

AF XY:

0.00951

AC XY:

1217

AN XY:

127984

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00363

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.00712

Gnomad NFE exome

AF:

0.00974

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.00923

AC:

13440

AN:

1456280

Hom.:

104

Cov.:

AF XY:

0.00960

AC XY:

6947

AN XY:

723988

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.00446

Gnomad4 ASJ exome

AF:

0.0264

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.00713

Gnomad4 NFE exome

AF:

0.00913

Gnomad4 OTH exome

AF:

0.00999

GnomAD4 genome

AF:

0.00672

AC:

1023

AN:

152238

Hom.:

Cov.:

AF XY:

0.00671

AC XY:

499

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.00901

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00655

Hom.:

Bravo

AF:

0.00643

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00784

AC:

952

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

0.067

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.86

.;D

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.18

Sift

Benign

0.036

D;D

Sift4G

Benign

0.27

T;T

Polyphen

0.34

B;B

Vest4

0.40

MVP

0.80

MPC

0.76

ClinPred

0.022

GERP RS

5.4

Varity_R

0.069

gMVP

0.24

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