rs2292573

Positions:

• chr11-78342093-A-G
• chr11-78342093-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-61192T>C		intron_variant		ENST00000361507.5	NP_536739.1
GAB2	XM_024448782.2	c.21+12641T>C		intron_variant			XP_024304550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-61192T>C		intron_variant		1	NM_080491.3	ENSP00000354952	P1
	ENST00000534168.1	n.35+17301A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.249

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

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

LitVar

Other links and lift over

dbSNP: rs2292573; hg19: chr11-78053139;