rs1893447

chr11-78262136-A-Gchr11-78262136-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.377-11736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,030 control chromosomes in the GnomAD database, including 5,867 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 0.26 (5867 hom., cov: 31)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB2	NM_080491.3	c.377-11736T>C		intron_variant		ENST00000361507.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB2	ENST00000361507.5	c.377-11736T>C		intron_variant		1	NM_080491.3	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39013 AN: 151910 Hom.: 5848 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.257 AC: 39074 AN: 152030 Hom.: 5867 Cov.: 31 AF XY: 0.259 AC XY: 19248 AN XY: 74286

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.253

Alfa AF: 0.204 Hom.: 1800

Bravo AF: 0.270

Asia WGS AF: 0.292 AC: 1014 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	4.4
Dann	Benign	0.52

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: rs1893447; hg19: chr11-77973182;