rs1257721773
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_000548.5(TSC2):c.484G>A(p.Asp162Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000372 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. D162E) has been classified as Likely benign.
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.484G>A | p.Asp162Asn | missense_variant, splice_region_variant | 6/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.484G>A | p.Asp162Asn | missense_variant, splice_region_variant | 6/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727206
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74362
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 | Oct 24, 2023 | - - |
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | This missense variant replaces aspartic acid with asparagine at codon 162 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 been identified in 2/282880 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at