NM_080491.3:c.76-61192T>C

Variant names:

• chr11-78342093-A-G
• rs2292573
• NM_080491.3:c.76-61192T>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.76-61192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,154 control chromosomes in the GnomAD database, including 5,138 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 0.25 (5138 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• 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]

ENSG00000288853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-61192T>C		intron_variant	Intron 1 of 9	ENST00000361507.5	NP_536739.1
GAB2	XM_024448782.2	c.21+12641T>C		intron_variant	Intron 1 of 9		XP_024304550.1
GAB2	NM_012296.4	c.-373T>C		upstream_gene_variant			NP_036428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-61192T>C		intron_variant	Intron 1 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37444 AN: 152038 Hom.: 5124 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.246 AC: 37493 AN: 152154 Hom.: 5138 Cov.: 32 AF XY: 0.250 AC XY: 18588 AN XY: 74366

African (AFR) AF: 0.341 AC: 14161 AN: 41502

American (AMR) AF: 0.278 AC: 4243 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2128 AN: 5180

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4822

European-Finnish (FIN) AF: 0.204 AC: 2158 AN: 10594

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11595 AN: 67982

Other (OTH) AF: 0.249 AC: 525 AN: 2110

Alfa AF: 0.210 Hom.: 1004

Bravo AF: 0.255

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.085
PromoterAI		-0.0010	Neutral
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: rs2292573; hg19: chr11-78053139;