11-78232411-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080491.3(GAB2):​c.621-5360A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,132 control chromosomes in the GnomAD database, including 3,109 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 ( 3109 hom., cov: 32)

Consequence

GAB2
NM_080491.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.346
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
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 rank MANE Protein UniProt
GAB2NM_080491.3 linkc.621-5360A>C intron_variant Intron 3 of 9 ENST00000361507.5 NP_536739.1 Q9UQC2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAB2ENST00000361507.5 linkc.621-5360A>C intron_variant Intron 3 of 9 1 NM_080491.3 ENSP00000354952.4 Q9UQC2-1
GAB2ENST00000340149.6 linkc.507-5360A>C intron_variant Intron 3 of 9 1 ENSP00000343959.2 Q9UQC2-2
GAB2ENST00000526030.1 linkn.556-5360A>C intron_variant Intron 3 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.195
AC:
29580
AN:
152014
Hom.:
3107
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.193
Gnomad AMI
AF:
0.0670
Gnomad AMR
AF:
0.248
Gnomad ASJ
AF:
0.194
Gnomad EAS
AF:
0.396
Gnomad SAS
AF:
0.280
Gnomad FIN
AF:
0.201
Gnomad MID
AF:
0.244
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.204
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.195
AC:
29593
AN:
152132
Hom.:
3109
Cov.:
32
AF XY:
0.198
AC XY:
14710
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.193
Gnomad4 AMR
AF:
0.248
Gnomad4 ASJ
AF:
0.194
Gnomad4 EAS
AF:
0.397
Gnomad4 SAS
AF:
0.280
Gnomad4 FIN
AF:
0.201
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.201
Alfa
AF:
0.197
Hom.:
600
Bravo
AF:
0.198
Asia WGS
AF:
0.275
AC:
953
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
10
DANN
Benign
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2450130; hg19: chr11-77943457; API