chr16-2088543-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_000548.5(TSC2):c.5357C>T(p.Pro1786Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,822 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. P1786S) 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.5357C>T | p.Pro1786Leu | missense_variant | 42/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5357C>T | p.Pro1786Leu | missense_variant | 42/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249104Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135274
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459822Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726244
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 28, 2024 | The p.P1786L variant (also known as c.5357C>T), located in coding exon 41 of the TSC2 gene, results from a C to T substitution at nucleotide position 5357. The proline at codon 1786 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 09, 2022 | - - |
Isolated focal cortical dysplasia type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 10, 2023 | - - |
Tuberous sclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at