rs2510038

Variant names:

• chr11-78254988-G-A
• rs2510038
• NM_080491.3:c.377-4588C>T

Variant summary

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

The NM_080491.3(GAB2):​c.377-4588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,736 control chromosomes in the GnomAD database, including 2,365 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 0.16 (2365 hom., cov: 31)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.377-4588C>T		intron_variant	Intron 2 of 9	ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.377-4588C>T		intron_variant	Intron 2 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23590 AN: 151616 Hom.: 2363 Cov.: 31

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.156 AC: 23604 AN: 151736 Hom.: 2365 Cov.: 31 AF XY: 0.160 AC XY: 11894 AN XY: 74118

African (AFR) AF: 0.0596 AC: 2468 AN: 41404

American (AMR) AF: 0.234 AC: 3560 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2041 AN: 5140

South Asian (SAS) AF: 0.278 AC: 1333 AN: 4794

European-Finnish (FIN) AF: 0.201 AC: 2108 AN: 10476

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10962 AN: 67908

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.152 Hom.: 326

Bravo AF: 0.154

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.62
PhyloP100		-0.62
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: rs2510038; hg19: chr11-77966034;