Genetic Variant GAB2:c.75+37542G>A (chr11-78380104-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_080491.3(GAB2):c.75+37542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene GAB2 is a known oncogene (CancerMine: 14 oncogene, 6 driver citations). The gene GAB2 is a cancer driver gene (CancerMine: 14 oncogene, 6 driver citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

GAB2
NM_080491.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

Publications

0 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:

ENSG00000288853 (HGNC:):

ENSG00000288853 links:

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new If you want to explore the variant's impact on the transcript NM_080491.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_080491.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	GAB2 NM_080491.3	MANE Select	c.75+37542G>A	intron	Intron 1 of 9	Prot: NP_536739.1 UniProt: Q9UQC2-1

GAB2 NM_080491.3

MANE Select

HGVSc / HGVSpc.75+37542G>A

Exon rankIntron 1 of 9

intron

Prot: NP_536739.1UniProt: Q9UQC2-1

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
GAB2 ENST00000361507.5	TSL:1MANE Select	c.75+37542G>A	intron	Intron 1 of 9	Prot: ENSP00000354952.4 UniProt: Q9UQC2-1
GAB2 ENST00000528886.5	TSL:4	c.-40+38133G>A	intron	Intron 1 of 2	Prot: ENSP00000433762.1 UniProt: E9PJE2
GAB2 ENST00000530915.1	TSL:4	c.-127-16001G>A	intron	Intron 1 of 3	Prot: ENSP00000431868.1 UniProt: E9PJ26

GAB2 ENST00000361507.5

TSL:1MANE Select

HGVSc / HGVSpc.75+37542G>A

Exon rankIntron 1 of 9

intron

Prot: ENSP00000354952.4UniProt: Q9UQC2-1

GAB2 ENST00000528886.5

TSL:4

HGVSc / HGVSpc.-40+38133G>A

Exon rankIntron 1 of 2

intron

Prot: ENSP00000433762.1UniProt: E9PJE2

GAB2 ENST00000530915.1

TSL:4

HGVSc / HGVSpc.-127-16001G>A

Exon rankIntron 1 of 3

intron

Prot: ENSP00000431868.1UniProt: E9PJ26

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	2.1
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.94
GPN-Star LLR	N/A	2.1
GPN-Star score	N/A	-2.0
PhyloP100	Benign	0.66

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence