16-2077723-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_000548.5(TSC2):c.2963G>A(p.Arg988His) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,612,520 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R988C) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.2963G>A | p.Arg988His | missense_variant | 26/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.2963G>A | p.Arg988His | missense_variant | 26/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250026Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135592
GnomAD4 exome AF: 0.0000459 AC: 67AN: 1460184Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27AN XY: 726426
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2024 | The p.R988H variant (also known as c.2963G>A), located in coding exon 25 of the TSC2 gene, results from a G to A substitution at nucleotide position 2963. The arginine at codon 988 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | May 24, 2021 | - - |
Tuberous sclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at