chr16-2088227-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP6BS2
The NM_000548.5(TSC2):āc.5161A>Gā(p.Met1721Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. M1721L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense, splice_region
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.5161A>G | p.Met1721Val | missense_variant, splice_region_variant | 41/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5161A>G | p.Met1721Val | missense_variant, splice_region_variant | 41/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250752Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135790
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460876Hom.: 0 Cov.: 35 AF XY: 0.0000275 AC XY: 20AN XY: 726710
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 17, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2023 | The p.M1721V variant (also known as c.5161A>G), located in coding exon 40 of the TSC2 gene, results from a A to G substitution at nucleotide position 5161. This variant impacts the first base pair of coding exon 40. The methionine at codon 1721 is replaced by valine, an amino acid with highly similar 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. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2021 | - - |
Tuberous sclerosis 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at