11-78229339-T-C

Position:

• chr11-78229339-T-C

Variant summary

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

The NM_080491.3(GAB2):​c.621-2288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,978 control chromosomes in the GnomAD database, including 3,098 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 0.19 (3098 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.621-2288A>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.621-2288A>G		intron_variant		1	NM_080491.3	ENSP00000354952	P1
GAB2	ENST00000340149.6	c.507-2288A>G		intron_variant		1		ENSP00000343959
GAB2	ENST00000526030.1	n.556-2288A>G		intron_variant, non_coding_transcript_variant		3
GAB2	ENST00000528329.1	n.125-2288A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29488 AN: 151858 Hom.: 3097 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.194 AC: 29500 AN: 151978 Hom.: 3098 Cov.: 32 AF XY: 0.198 AC XY: 14671 AN XY: 74278

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.201

Alfa AF: 0.178 Hom.: 1280

Bravo AF: 0.197

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.79
DANN	Benign	0.79

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: rs2450129; hg19: chr11-77940385;