11-78230030-T-C

Position:

• chr11-78230030-T-C

Variant summary

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

The ENST00000361507.5(GAB2):​c.621-2979A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,170 control chromosomes in the GnomAD database, including 8,706 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 0.30 (8706 hom., cov: 33)
• Consequence: GAB2 ENST00000361507.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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:20061): (ubiquitin specific peptidase 35) This gene encodes a member of the peptidase C19 family of ubiquitin-specific proteases. These deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin proteins from other proteins. The encoded protein associates with polarized mitochondria and has been shown to inhibit NF-kappa B activation and delay PARK2-mediated degradation of mitochondria. Expression of this gene is upregulated by the let-7a microRNA and reduced expression has been observed in human tumor tissues. [provided by RefSeq, Jul 2017]

GAB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.621-2979A>G		intron_variant		ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.621-2979A>G		intron_variant		1	NM_080491.3	ENSP00000354952.4
GAB2	ENST00000340149.6	c.507-2979A>G		intron_variant		1		ENSP00000343959.2
GAB2	ENST00000526030.1	n.556-2979A>G		intron_variant		3
GAB2	ENST00000528329.1	n.124+1779A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44882 AN: 152052 Hom.: 8682 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.295 AC: 44965 AN: 152170 Hom.: 8706 Cov.: 33 AF XY: 0.297 AC XY: 22098 AN XY: 74392

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.278

Alfa AF: 0.201 Hom.: 4088

Bravo AF: 0.313

Asia WGS AF: 0.302 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.30
DANN	Benign	0.43

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: rs1007837; hg19: chr11-77941076;