rs876659087
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000548.5(TSC2):āc.3981C>Gā(p.Asp1327Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. D1327G) 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.3981C>G | p.Asp1327Glu | missense_variant | 33/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.3981C>G | p.Asp1327Glu | missense_variant | 33/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459212Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725744
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2019 | The p.D1327E variant (also known as c.3981C>G), located in coding exon 32 of the TSC2 gene, results from a C to G substitution at nucleotide position 3981. The aspartic acid at codon 1327 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in limited sequence alignment. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at