11-78324810-G-T

Variant names:

• chr11-78324810-G-T
• rs2458640
• NM_080491.3:c.76-43909C>A

Variant summary

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

The NM_080491.3(GAB2):​c.76-43909C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,120 control chromosomes in the GnomAD database, including 28,669 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 0.56 (28667 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-43909C>A		intron_variant	Intron 1 of 9	ENST00000361507.5	NP_536739.1
GAB2	NM_012296.4	c.-40+16950C>A		intron_variant	Intron 1 of 9		NP_036428.1
GAB2	XM_024448782.2	c.21+29924C>A		intron_variant	Intron 1 of 9		XP_024304550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-43909C>A		intron_variant	Intron 1 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85113 AN: 151996 Hom.: 28672 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.560 AC: 85116 AN: 152114 Hom.: 28667 Cov.: 32 AF XY: 0.551 AC XY: 40996 AN XY: 74350

African (AFR) AF: 0.206 AC: 8552 AN: 41452

American (AMR) AF: 0.609 AC: 9302 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2265 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1197 AN: 5184

South Asian (SAS) AF: 0.427 AC: 2055 AN: 4818

European-Finnish (FIN) AF: 0.635 AC: 6719 AN: 10584

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52835 AN: 68006

Other (OTH) AF: 0.582 AC: 1230 AN: 2114

Alfa AF: 0.686 Hom.: 58973

Bravo AF: 0.545

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.57
DANN	Benign	0.72
PhyloP100		-0.52
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: rs2458640; hg19: chr11-78035856;