dbSNP rs3740677: GAB2:c.*2282C>A (chr11-78216990-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080491.3(GAB2):c.*2282C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,166 control chromosomes in the GnomAD database, including 29,140 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 0.57 ( 29105 hom., cov: 31)

Exomes 𝑓: 0.75 ( 35 hom. )

Consequence

GAB2
NM_080491.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.482

Publications

23 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3 link	c.*2282C>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000361507.5	NP_536739.1	Q9UQC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5 link	c.*2282C>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_080491.3	ENSP00000354952.4		Q9UQC2-1
GAB2	ENST00000340149.6 link	c.*2282C>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000343959.2		Q9UQC2-2

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87059

AN:

151922

Hom.:

29108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.890

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.775

Gnomad OTH

AF:

0.594

GnomAD4 exome

AF:

0.746

AC:

AN:

126

Hom.:

Cov.:

AF XY:

0.745

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.826

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.573

AC:

87060

AN:

152040

Hom.:

29105

Cov.:

AF XY:

0.565

AC XY:

41982

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.247

AC:

10247

AN:

41446

American (AMR)

AF:

0.608

AC:

9291

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

2284

AN:

3464

East Asian (EAS)

AF:

0.257

AC:

1328

AN:

5176

South Asian (SAS)

AF:

0.410

AC:

1975

AN:

4822

European-Finnish (FIN)

AF:

0.661

AC:

6989

AN:

10566

Middle Eastern (MID)

AF:

0.634

AC:

185

AN:

292

European-Non Finnish (NFE)

AF:

0.775

AC:

52708

AN:

67972

Other (OTH)

AF:

0.590

AC:

1243

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1482

2964

4445

5927

7409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.712

Hom.:

63016

Bravo

AF:

0.557

Asia WGS

AF:

0.310

AC:

1080

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.69

PhyloP100

0.48

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over