16-2084574-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000548.5(TSC2):c.4352G>A(p.Arg1451His) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,607,104 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. R1451C) 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.4352G>A | p.Arg1451His | missense_variant | 34/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4352G>A | p.Arg1451His | missense_variant | 34/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152218Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000376 AC: 9AN: 239510Hom.: 0 AF XY: 0.0000228 AC XY: 3AN XY: 131514
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1454886Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 724062
GnomAD4 genome AF: 0.000105 AC: 16AN: 152218Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9AN XY: 74356
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 25, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at