Variant chr22-39968048-C-T 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.466C>T(p.Arg156Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,611,954 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 14 hom. )

Consequence

GRAP2
NM_004810.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005938649).

BP6

Variant 22-39968048-C-T is Benign according to our data. Variant chr22-39968048-C-T is described in ClinVar as [Benign]. Clinvar id is 724441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAP2	NM_004810.4 linkuse as main transcript	c.466C>T	p.Arg156Trp	missense_variant	6/8	ENST00000344138.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAP2	ENST00000344138.9 linkuse as main transcript	c.466C>T	p.Arg156Trp	missense_variant	6/8	1	NM_004810.4	P1	O75791-1
GRAP2	ENST00000407075.3 linkuse as main transcript	c.466C>T	p.Arg156Trp	missense_variant	5/7	1		P1	O75791-1
GRAP2	ENST00000481263.1 linkuse as main transcript	n.116C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

591

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00123

AC:

303

AN:

246830

Hom.:

AF XY:

0.00108

AC XY:

144

AN XY:

133594

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000265

Gnomad FIN exome

AF:

0.0000477

Gnomad NFE exome

AF:

0.000287

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.000649

AC:

948

AN:

1459674

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

474

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000373

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152280

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000895

Hom.:

Bravo

AF:

0.00481

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.81

.;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.030

Sift

Benign

0.077

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.15

B;B

Vest4

0.32

MVP

0.82

MPC

0.41

ClinPred

0.021

GERP RS

0.27

Varity_R

0.059

gMVP

0.33

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