rs759882146
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_000548.5(TSC2):āc.4469A>Gā(p.Glu1490Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,598,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1490D) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.4469A>G | p.Glu1490Gly | missense_variant | 34/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4469A>G | p.Glu1490Gly | missense_variant | 34/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152042Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000190 AC: 45AN: 237262Hom.: 0 AF XY: 0.000185 AC XY: 24AN XY: 129854
GnomAD4 exome AF: 0.0000290 AC: 42AN: 1446220Hom.: 0 Cov.: 33 AF XY: 0.0000306 AC XY: 22AN XY: 719850
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152042Hom.: 0 Cov.: 34 AF XY: 0.0000673 AC XY: 5AN XY: 74266
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 10, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 15, 2021 | - - |
Ovarian cancer Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at