11-78299784-A-G

Variant names:

• chr11-78299784-A-G
• rs11602622
• NM_080491.3:c.76-18883T>C

Variant summary

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

The NM_080491.3(GAB2):​c.76-18883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,130 control chromosomes in the GnomAD database, including 3,582 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 0.21 (3582 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 21 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]

ENSG00000288853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-18883T>C		intron_variant	Intron 1 of 9	ENST00000361507.5	NP_536739.1
GAB2	NM_012296.4	c.-39-18883T>C		intron_variant	Intron 1 of 9		NP_036428.1
GAB2	XM_024448782.2	c.22-18883T>C		intron_variant	Intron 1 of 9		XP_024304550.1
LOC105369402	XR_950343.4	n.322+2699A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-18883T>C		intron_variant	Intron 1 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31578 AN: 152010 Hom.: 3577 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.208 AC: 31598 AN: 152130 Hom.: 3582 Cov.: 32 AF XY: 0.211 AC XY: 15705 AN XY: 74364

African (AFR) AF: 0.235 AC: 9774 AN: 41506

American (AMR) AF: 0.257 AC: 3926 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2080 AN: 5166

South Asian (SAS) AF: 0.296 AC: 1427 AN: 4822

European-Finnish (FIN) AF: 0.200 AC: 2118 AN: 10572

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11031 AN: 68002

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.182 Hom.: 3495

Bravo AF: 0.214

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.81
PhyloP100		-0.044
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: rs11602622; hg19: chr11-78010830;