Variant rs1385600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_080491.3(GAB2):c.1290T>C(p.Val430Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,608,886 control chromosomes in the GnomAD database, including 38,069 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 0.27 ( 6531 hom., cov: 32)

Exomes 𝑓: 0.19 ( 31538 hom. )

Consequence

GAB2
NM_080491.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

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:

ENSG00000288538 (HGNC:):

ENSG00000288538 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=2.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3 link	c.1290T>C	p.Val430Val	synonymous_variant	5/10	ENST00000361507.5	NP_536739.1	Q9UQC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GAB2	ENST00000361507.5 link	c.1290T>C	p.Val430Val	synonymous_variant	5/10	1	NM_080491.3	ENSP00000354952.4	Q9UQC2-1
GAB2	ENST00000340149.6 link	c.1176T>C	p.Val392Val	synonymous_variant	5/10	1		ENSP00000343959.2	Q9UQC2-2
ENSG00000288538	ENST00000656562.1 link	n.964A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40719

AN:

151916

Hom.:

6514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.248

AC:

62319

AN:

251118

Hom.:

9040

AF XY:

0.240

AC XY:

32615

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.386

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.192

AC:

279641

AN:

1456850

Hom.:

31538

Cov.:

AF XY:

0.193

AC XY:

140049

AN XY:

724998

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.350

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.268

AC:

40787

AN:

152036

Hom.:

6531

Cov.:

AF XY:

0.270

AC XY:

20071

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.439

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.190

Hom.:

6610

Bravo

AF:

0.282

Asia WGS

AF:

0.295

AC:

1024

AN:

3478

EpiCase

AF:

0.165

EpiControl

AF:

0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over