chr16-2058762-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP6BS2
The NM_000548.5(TSC2):āc.864C>Gā(p.Asp288Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000379 in 1,584,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D288N) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.864C>G | p.Asp288Glu | missense_variant | 10/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.864C>G | p.Asp288Glu | missense_variant | 10/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000349 AC: 5AN: 1432300Hom.: 0 Cov.: 32 AF XY: 0.00000423 AC XY: 3AN XY: 709526
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 02, 2023 | This missense variant replaces aspartic acid with glutamic acid at codon 288 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2022 | The p.D288E variant (also known as c.864C>G), located in coding exon 9 of the TSC2 gene, results from a C to G substitution at nucleotide position 864. The aspartic acid at codon 288 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 | Aug 04, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at