rs2373115

Variant names:

• chr11-78380104-C-A
• rs2373115
• NM_080491.3:c.75+37542G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-78380104-C-A
• chr11-78380104-C-G
• chr11-78380104-C-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.75+37542G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,114 control chromosomes in the GnomAD database, including 4,857 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 0.24 (4857 hom., cov: 33)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 97 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]

ENSG00000288853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	NM_080491.3	MANE Select	c.75+37542G>T		intron	N/A	NP_536739.1	Q9UQC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	ENST00000361507.5	TSL:1 MANE Select	c.75+37542G>T		intron	N/A	ENSP00000354952.4	Q9UQC2-1
	GAB2	ENST00000528886.5	TSL:4	c.-40+38133G>T		intron	N/A	ENSP00000433762.1	E9PJE2
	GAB2	ENST00000530915.1	TSL:4	c.-127-16001G>T		intron	N/A	ENSP00000431868.1	E9PJ26

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36410 AN: 151996 Hom.: 4836 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.240 AC: 36480 AN: 152114 Hom.: 4857 Cov.: 33 AF XY: 0.244 AC XY: 18166 AN XY: 74354

African (AFR) AF: 0.318 AC: 13201 AN: 41494

American (AMR) AF: 0.277 AC: 4233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2115 AN: 5176

South Asian (SAS) AF: 0.303 AC: 1460 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2151 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11570 AN: 68000

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.199 Hom.: 11389

Bravo AF: 0.248

Asia WGS AF: 0.306 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.91
DANN	Benign	0.27
PhyloP100		0.66
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: rs2373115; hg19: chr11-78091150;