16-2070555-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBP6BS2
The NM_000548.5(TSC2):āc.1816A>Gā(p.Ile606Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000998 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. I606F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.1816A>G | p.Ile606Val | missense_variant | 17/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.1816A>G | p.Ile606Val | missense_variant | 17/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250436Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135772
GnomAD4 exome AF: 0.000106 AC: 155AN: 1460824Hom.: 0 Cov.: 34 AF XY: 0.0000963 AC XY: 70AN XY: 726716
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 23, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 30, 2020 | 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 22, 2021 | - - |
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 17, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23514105, 29641532) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at