16-2056652-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000548.5(TSC2):c.657G>A(p.Leu219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,458,694 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L219L) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.657G>A | p.Leu219= | synonymous_variant | 8/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.657G>A | p.Leu219= | synonymous_variant | 8/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249086Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134938
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1458694Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 725864
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 30, 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