rs36032671
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_000548.5(TSC2):c.*61_*62del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0859 in 1,547,878 control chromosomes in the GnomAD database, including 6,372 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.065 ( 439 hom., cov: 32)
Exomes 𝑓: 0.088 ( 5933 hom. )
Consequence
TSC2
NM_000548.5 3_prime_UTR
NM_000548.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.51
Genes affected
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
?
Variant 16-2088669-TAA-T is Benign according to our data. Variant chr16-2088669-TAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 50172.We mark this variant Likely_benign, oryginal submissions are: {not_provided=2, Uncertain_significance=1, Benign=1}. Variant chr16-2088669-TAA-T is described in Lovd as [Benign]. Variant chr16-2088669-TAA-T is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.*61_*62del | 3_prime_UTR_variant | 42/42 | ENST00000219476.9 | ||
PKD1 | NM_001009944.3 | downstream_gene_variant | ENST00000262304.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.*61_*62del | 3_prime_UTR_variant | 42/42 | 5 | NM_000548.5 | |||
PKD1 | ENST00000262304.9 | downstream_gene_variant | 1 | NM_001009944.3 | P5 |
Frequencies
GnomAD3 genomes ? AF: 0.0654 AC: 9902AN: 151502Hom.: 439 Cov.: 32
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GnomAD4 exome AF: 0.0882 AC: 123139AN: 1396260Hom.: 5933 AF XY: 0.0874 AC XY: 60431AN XY: 691458
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GnomAD4 genome ? AF: 0.0653 AC: 9899AN: 151618Hom.: 439 Cov.: 32 AF XY: 0.0666 AC XY: 4938AN XY: 74128
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3Other:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1Other:1
not provided, no classification provided | curation | Tuberous sclerosis database (TSC2) | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | - - |
Tuberous sclerosis syndrome;C0751674:Lymphangiomyomatosis Other:1
not provided, no classification provided | curation | Tuberous sclerosis database (TSC2) | - | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at