11-78250429-A-G

Position:

• chr11-78250429-A-G

Variant summary

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

The ENST00000361507.5(GAB2):​c.377-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,603,300 control chromosomes in the GnomAD database, including 193 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.019 (107 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (86 hom.)
• Consequence: GAB2 ENST00000361507.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.377-29T>C		intron_variant		ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.377-29T>C		intron_variant		1	NM_080491.3	ENSP00000354952	P1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2944 AN: 152082 Hom.: 106 Cov.: 31

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00527 AC: 1317 AN: 250118 Hom.: 51 AF XY: 0.00395 AC XY: 535 AN XY: 135298

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00195 AC: 2833 AN: 1451100 Hom.: 86 Cov.: 28 AF XY: 0.00168 AC XY: 1216 AN XY: 722268

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.00226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000717

Gnomad4 OTH exome AF: 0.00413

GnomAD4 genome AF: 0.0194 AC: 2959 AN: 152200 Hom.: 107 Cov.: 31 AF XY: 0.0187 AC XY: 1391 AN XY: 74434

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00992 Hom.: 10

Bravo AF: 0.0224

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.51
BranchPoint Hunter		1.0

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: rs11237429; hg19: chr11-77961475;