rs373818076
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PM1PM5BP4_StrongBP6_Very_StrongBS2
The NM_000548.5(TSC2):c.814G>A(p.Ala272Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000902 in 1,551,706 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A272S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.814G>A | p.Ala272Thr | missense_variant | 9/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.814G>A | p.Ala272Thr | missense_variant | 9/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152170Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000198 AC: 31AN: 156822Hom.: 1 AF XY: 0.000206 AC XY: 17AN XY: 82554
GnomAD4 exome AF: 0.0000893 AC: 125AN: 1399418Hom.: 0 Cov.: 32 AF XY: 0.0000869 AC XY: 60AN XY: 690226
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74454
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2015 | 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 25, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Lymphangiomyomatosis;C1846385:Isolated focal cortical dysplasia type II;C1860707:Tuberous sclerosis 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 15, 2021 | - - |
TSC2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 14, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at