rs901104

chr11-78219453-G-Achr11-78219453-G-T

Variant summary

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

The NM_080491.3(GAB2):c.1888-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,602,208 control chromosomes in the GnomAD database, including 28,443 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 0.16 (2353 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26090 hom.)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB2	NM_080491.3	c.1888-38C>T		intron_variant		ENST00000361507.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB2	ENST00000361507.5	c.1888-38C>T		intron_variant		1	NM_080491.3	P1
GAB2	ENST00000340149.6	c.1774-38C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23632 AN: 151998 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.216 AC: 53324 AN: 246502 Hom.: 6904 AF XY: 0.216 AC XY: 28838 AN XY: 133202

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.379

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.177 AC: 256655 AN: 1450092 Hom.: 26090 Cov.: 28 AF XY: 0.180 AC XY: 129820 AN XY: 721740

Gnomad4 AFR exome AF: 0.0581

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.155 AC: 23647 AN: 152116 Hom.: 2353 Cov.: 32 AF XY: 0.160 AC XY: 11929 AN XY: 74344

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.172

Alfa AF: 0.173 Hom.: 692

Bravo AF: 0.154

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	12
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs901104; hg19: chr11-77930499; COSMIC: COSV104413130; COSMIC: COSV104413130;