16-2088270-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 4P and 11B. PM1PM5BP4_ModerateBP6BS1BS2
The NM_000548.5(TSC2):āc.5204T>Cā(p.Ile1735Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000049 in 1,612,946 control chromosomes in the GnomAD database, including 1 homozygotes. 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. I1735V) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.5204T>C | p.Ile1735Thr | missense_variant | 41/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5204T>C | p.Ile1735Thr | missense_variant | 41/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152186Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.0000918 AC: 23AN: 250616Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135772
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460760Hom.: 0 Cov.: 35 AF XY: 0.0000179 AC XY: 13AN XY: 726650
GnomAD4 genome AF: 0.000322 AC: 49AN: 152186Hom.: 1 Cov.: 34 AF XY: 0.000511 AC XY: 38AN XY: 74344
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 27, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2021 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at