11-78334025-G-C

Position:

• chr11-78334025-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080491.3(GAB2):​c.76-53124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,070 control chromosomes in the GnomAD database, including 6,420 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 0.27 (6420 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-53124C>G		intron_variant		ENST00000361507.5	NP_536739.1
GAB2	NM_012296.4	c.-40+7735C>G		intron_variant			NP_036428.1
GAB2	XM_024448782.2	c.21+20709C>G		intron_variant			XP_024304550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-53124C>G		intron_variant		1	NM_080491.3	ENSP00000354952	P1
	ENST00000534168.1	n.35+9233G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40721 AN: 151952 Hom.: 6400 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.268 AC: 40788 AN: 152070 Hom.: 6420 Cov.: 32 AF XY: 0.271 AC XY: 20132 AN XY: 74326

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.269

Alfa AF: 0.115 Hom.: 183

Bravo AF: 0.281

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.055
DANN	Benign	0.34

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: rs7115850; hg19: chr11-78045071;