rs751990617
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP6
The NM_000548.5(TSC2):c.5200G>A(p.Asp1734Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1734E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.5200G>A | p.Asp1734Asn | missense_variant | 41/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5200G>A | p.Asp1734Asn | missense_variant | 41/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250576Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135740
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1460768Hom.: 0 Cov.: 35 AF XY: 0.0000317 AC XY: 23AN XY: 726656
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genomics Laboratory, Washington University in St. Louis | Aug 06, 2023 | The TSC2 c.5200G>A (p.Asp1734Asn) variant has been reported in one individual affected with colorectal cancer (Zhang JX et al., PMID: 25892863). This variant has been classified in the ClinVar database as likely benign by two submitters and uncertain significance by one submitter (ClinVar ID 536037). TSC2 c.5200G>A (p.Asp1734Asn) is only observed on 4/152196 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to TSC2 protein function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2022 | The c.5200G>A (p.D1734N) alteration is located in exon 41 (coding exon 40) of the TSC2 gene. This alteration results from a G to A substitution at nucleotide position 5200, causing the aspartic acid (D) at amino acid position 1734 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at