11-78216990-G-T

Position:

• chr11-78216990-G-T

Variant summary

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

The ENST00000361507.5(GAB2):​c.*2282C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,166 control chromosomes in the GnomAD database, including 29,140 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 0.57 (29105 hom., cov: 31)
  • Exomes 𝑓: 0.75 (35 hom.)
• Consequence: GAB2 ENST00000361507.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482

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]

USP35 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.*2282C>A		3_prime_UTR_variant	10/10	ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.*2282C>A		3_prime_UTR_variant	10/10	1	NM_080491.3	ENSP00000354952	P1
GAB2	ENST00000340149.6	c.*2282C>A		3_prime_UTR_variant	10/10	1		ENSP00000343959

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87059 AN: 151922 Hom.: 29108 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.746 AC: 94 AN: 126 Hom.: 35 Cov.: 0 AF XY: 0.745 AC XY: 70 AN XY: 94

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.826

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.573 AC: 87060 AN: 152040 Hom.: 29105 Cov.: 31 AF XY: 0.565 AC XY: 41982 AN XY: 74336

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.590

Alfa AF: 0.725 Hom.: 44287

Bravo AF: 0.557

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.69

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: rs3740677; hg19: chr11-77928036;