rs773786955
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM5BP4_ModerateBP6BS2
The NM_000548.5(TSC2):c.2364G>A(p.Met788Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,459,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. M788R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.2364G>A | p.Met788Ile | missense_variant | 22/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.2364G>A | p.Met788Ile | missense_variant | 22/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248996Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135164
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1459086Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 725902
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Apr 27, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2021 | The p.M788I variant (also known as c.2364G>A), located in coding exon 21 of the TSC2 gene, results from a G to A substitution at nucleotide position 2364. The methionine at codon 788 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Tuberous sclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at