rs767626323
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000548.5(TSC2):c.202G>A(p.Ala68Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,604 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. A68P) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.202G>A | p.Ala68Thr | missense_variant | 3/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.202G>A | p.Ala68Thr | missense_variant | 3/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251046Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461562Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727070
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74274
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 | Nov 02, 2023 | This missense variant replaces alanine with threonine at codon 68 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with cortical dysplasias and TSC-associated neuropsychiatric disorders (TAND) in the literature (PMID: 32917966). This variant has been identified in 1/251046 chromosomes 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 | Sep 14, 2022 | The p.A68T variant (also known as c.202G>A), located in coding exon 2 of the TSC2 gene, results from a G to A substitution at nucleotide position 202. The alanine at codon 68 is replaced by threonine, an amino acid with similar properties. This alteration was identified in an individual with findings suggestive of tuberous sclerosis (Meng Y et al. J Hum Genet, 2021 Mar;66:227-236). This amino acid position is highly 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. - |
Tuberous sclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at