Variant chr11-78222097-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_080491.3(GAB2):c.1658+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,577,812 control chromosomes in the GnomAD database, including 7 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 7 hom. )

Consequence

GAB2
NM_080491.3 splice_region, intron

Scores

Splicing: ADA: 0.00004840

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.642

Variant links:

Genes affected

GAB2 (HGNC:14458): (GRB2 associated binding protein 2) This gene is a member of the GRB2-associated binding protein (GAB) gene family. These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. Two alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

GAB2 links:

USP35 (HGNC:):

USP35 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 (BayesDel_noAF=-0.81).

BP6

Variant 11-78222097-G-A is Benign according to our data. Variant chr11-78222097-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 722439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB2	NM_080491.3 linkuse as main transcript	c.1658+8C>T		splice_region_variant, intron_variant		ENST00000361507.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB2	ENST00000361507.5 linkuse as main transcript	c.1658+8C>T		splice_region_variant, intron_variant		1	NM_080491.3	P1	Q9UQC2-1
GAB2	ENST00000340149.6 linkuse as main transcript	c.1544+8C>T		splice_region_variant, intron_variant		1			Q9UQC2-2

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00182

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00126

AC:

317

AN:

251344

Hom.:

AF XY:

0.00124

AC XY:

169

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00425

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00123

AC:

1760

AN:

1425626

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

885

AN XY:

711714

show subpopulations

Gnomad4 AFR exome

AF:

0.0000610

Gnomad4 AMR exome

AF:

0.000627

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152186

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

121

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.00182

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00118

EpiCase

AF:

0.00153

EpiControl

AF:

0.00113

ClinVar

Significance: Benign/Likely 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	clinical testing	Invitae	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	GAB2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0060

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