11-78226549-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_080491.3(GAB2):āc.1123A>Gā(p.Ile375Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,412,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_080491.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GAB2 | NM_080491.3 | c.1123A>G | p.Ile375Val | missense_variant | 4/10 | ENST00000361507.5 | NP_536739.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GAB2 | ENST00000361507.5 | c.1123A>G | p.Ile375Val | missense_variant | 4/10 | 1 | NM_080491.3 | ENSP00000354952 | P1 | |
GAB2 | ENST00000340149.6 | c.1009A>G | p.Ile337Val | missense_variant | 4/10 | 1 | ENSP00000343959 |
Frequencies
GnomAD3 genomes AF: 0.0000282 AC: 4AN: 141748Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251360Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135870
GnomAD4 exome AF: 0.0000464 AC: 59AN: 1270258Hom.: 0 Cov.: 34 AF XY: 0.0000428 AC XY: 27AN XY: 630282
GnomAD4 genome AF: 0.0000282 AC: 4AN: 141886Hom.: 0 Cov.: 30 AF XY: 0.0000145 AC XY: 1AN XY: 68890
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2023 | The c.1123A>G (p.I375V) alteration is located in exon 4 (coding exon 4) of the GAB2 gene. This alteration results from a A to G substitution at nucleotide position 1123, causing the isoleucine (I) at amino acid position 375 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at