chr16-2086353-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PP3_ModerateBP6BS2
The NM_000548.5(TSC2):āc.4823A>Gā(p.Tyr1608Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y1608N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.4823A>G | p.Tyr1608Cys | missense_variant | 37/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4823A>G | p.Tyr1608Cys | missense_variant | 37/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248738Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135102
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460570Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726596
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2022 | The p.Y1608C variant (also known as c.4823A>G), located in coding exon 36 of the TSC2 gene, results from an A to G substitution at nucleotide position 4823. The tyrosine at codon 1608 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Tuberous sclerosis 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at