chr11-78226612-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_080491.3(GAB2):c.1060C>T(p.Arg354Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,599,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
GAB2
NM_080491.3 missense
NM_080491.3 missense
Scores
4
9
4
Clinical Significance
Conservation
PhyloP100: 3.19
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAB2 | NM_080491.3 | c.1060C>T | p.Arg354Cys | missense_variant | 4/10 | ENST00000361507.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAB2 | ENST00000361507.5 | c.1060C>T | p.Arg354Cys | missense_variant | 4/10 | 1 | NM_080491.3 | P1 | |
GAB2 | ENST00000340149.6 | c.946C>T | p.Arg316Cys | missense_variant | 4/10 | 1 | |||
GAB2 | ENST00000528329.1 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000664 AC: 1AN: 150504Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249714Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135062
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GnomAD4 exome AF: 0.00000552 AC: 8AN: 1449404Hom.: 0 Cov.: 41 AF XY: 0.00000139 AC XY: 1AN XY: 721494
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GnomAD4 genome ? AF: 0.00000664 AC: 1AN: 150504Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1AN XY: 73400
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | The c.1060C>T (p.R354C) alteration is located in exon 4 (coding exon 4) of the GAB2 gene. This alteration results from a C to T substitution at nucleotide position 1060, causing the arginine (R) at amino acid position 354 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.18
.;Gain of glycosylation at S359 (P = 0.1135);
MVP
MPC
0.35
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at