11-78248613-G-A

Variant names:

• chr11-78248613-G-A
• rs2510054
• NM_080491.3:c.620+1544C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080491.3(GAB2):​c.620+1544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,086 control chromosomes in the GnomAD database, including 4,173 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 0.22 (4173 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.620+1544C>T		intron_variant	Intron 3 of 9	ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.620+1544C>T		intron_variant	Intron 3 of 9	1	NM_080491.3	ENSP00000354952.4
GAB2	ENST00000340149.6	c.506+1544C>T		intron_variant	Intron 3 of 9	1		ENSP00000343959.2
GAB2	ENST00000526030.1	n.556-21562C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33821 AN: 151968 Hom.: 4168 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.223 AC: 33860 AN: 152086 Hom.: 4173 Cov.: 32 AF XY: 0.225 AC XY: 16722 AN XY: 74346

African (AFR) AF: 0.292 AC: 12090 AN: 41452

American (AMR) AF: 0.257 AC: 3928 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2072 AN: 5182

South Asian (SAS) AF: 0.280 AC: 1352 AN: 4826

European-Finnish (FIN) AF: 0.201 AC: 2125 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11036 AN: 67986

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.188 Hom.: 3839

Bravo AF: 0.230

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.28
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2510054; hg19: chr11-77959659;