11-78269536-T-C

Variant names:

• chr11-78269536-T-C
• rs2511170
• NM_080491.3:c.376+11065A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080491.3(GAB2):​c.376+11065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,106 control chromosomes in the GnomAD database, including 3,313 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 0.20 (3313 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 14 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	NM_080491.3	MANE Select	c.376+11065A>G		intron	N/A	NP_536739.1	Q9UQC2-1
	GAB2	NM_012296.4		c.262+11065A>G		intron	N/A	NP_036428.1	Q9UQC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	ENST00000361507.5	TSL:1 MANE Select	c.376+11065A>G		intron	N/A	ENSP00000354952.4	Q9UQC2-1
	GAB2	ENST00000340149.6	TSL:1	c.262+11065A>G		intron	N/A	ENSP00000343959.2	Q9UQC2-2
	GAB2	ENST00000528886.5	TSL:4	c.262+11065A>G		intron	N/A	ENSP00000433762.1	E9PJE2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30469 AN: 151986 Hom.: 3311 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30493 AN: 152106 Hom.: 3313 Cov.: 32 AF XY: 0.204 AC XY: 15158 AN XY: 74374

African (AFR) AF: 0.211 AC: 8770 AN: 41492

American (AMR) AF: 0.252 AC: 3852 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2087 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2130 AN: 10576

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11009 AN: 67984

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.195 Hom.: 676

Bravo AF: 0.204

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2511170; hg19: chr11-77980582;