Variant chr22-39968035-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004810.4(GRAP2):c.460-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,611,490 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 3 hom. )

Consequence

GRAP2
NM_004810.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008189

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 22-39968035-C-T is Benign according to our data. Variant chr22-39968035-C-T is described in ClinVar as [Benign]. Clinvar id is 711087.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAP2	NM_004810.4 linkuse as main transcript	c.460-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000344138.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
GRAP2	ENST00000344138.9 linkuse as main transcript	c.460-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_004810.4	P1	O75791-1
GRAP2	ENST00000407075.3 linkuse as main transcript	c.460-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		P1	O75791-1
GRAP2	ENST00000481263.1 linkuse as main transcript	n.110-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

346

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00811

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000628

AC:

155

AN:

246898

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

133602

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000223

AC:

325

AN:

1459164

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

725478

show subpopulations

Gnomad4 AFR exome

AF:

0.00861

Gnomad4 AMR exome

AF:

0.000359

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.00227

AC:

346

AN:

152326

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00808

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00270

Asia WGS

AF:

0.000289

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

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.0

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00082

dbscSNV1_RF

Benign

0.028

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