chr16-2088517-T-C
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000548.5(TSC2):c.5331T>C(p.Pro1777Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant polycystic kidney diseaseInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- polycystic kidney disease 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- autosomal recessive polycystic kidney diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Caroli diseaseInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
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ACMG classification
Our verdict: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.5331T>C | p.Pro1777Pro | synonymous_variant | Exon 42 of 42 | 5 | NM_000548.5 | ENSP00000219476.3 | ||
PKD1 | ENST00000262304.9 | c.*1210A>G | downstream_gene_variant | 1 | NM_001009944.3 | ENSP00000262304.4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152060Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000160 AC: 4AN: 249840 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460418Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 726506 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74286 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:3
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Hereditary cancer-predisposing syndrome Benign:2
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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. -
Tuberous sclerosis syndrome Benign:1Other:1
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Lymphangiomyomatosis;C1846385:Isolated focal cortical dysplasia type II;C1860707:Tuberous sclerosis 2 Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at