Variant rs901104 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080491.3(GAB2):c.1888-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,602,208 control chromosomes in the GnomAD database, including 28,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2353 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26090 hom. )

Consequence

GAB2
NM_080491.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0650

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:20061): (ubiquitin specific peptidase 35) This gene encodes a member of the peptidase C19 family of ubiquitin-specific proteases. These deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin proteins from other proteins. The encoded protein associates with polarized mitochondria and has been shown to inhibit NF-kappa B activation and delay PARK2-mediated degradation of mitochondria. Expression of this gene is upregulated by the let-7a microRNA and reduced expression has been observed in human tumor tissues. [provided by RefSeq, Jul 2017]

USP35 links:

USP35 (HGNC:):

USP35 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3 linkuse as main transcript	c.1888-38C>T		intron_variant		ENST00000361507.5	NP_536739.1	Q9UQC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5 linkuse as main transcript	c.1888-38C>T		intron_variant		1	NM_080491.3	ENSP00000354952.4		Q9UQC2-1
GAB2	ENST00000340149.6 linkuse as main transcript	c.1774-38C>T		intron_variant		1		ENSP00000343959.2		Q9UQC2-2

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23632

AN:

151998

Hom.:

2350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.216

AC:

53324

AN:

246502

Hom.:

6904

AF XY:

0.216

AC XY:

28838

AN XY:

133202

show subpopulations

Gnomad AFR exome

AF:

0.0604

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.379

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.177

AC:

256655

AN:

1450092

Hom.:

26090

Cov.:

AF XY:

0.180

AC XY:

129820

AN XY:

721740

show subpopulations

Gnomad4 AFR exome

AF:

0.0581

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.178

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.155

AC:

23647

AN:

152116

Hom.:

2353

Cov.:

AF XY:

0.160

AC XY:

11929

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0609

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.393

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.173

Hom.:

692

Bravo

AF:

0.154

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over