Variant rs13335638 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000548.5(TSC2):c.4850-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,538,084 control chromosomes in the GnomAD database, including 33,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 8001 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25022 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -3.40

Variant links:

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]

TSC2 links:

TSC2 (HGNC:):

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-2086623-T-C is Benign according to our data. Variant chr16-2086623-T-C is described in ClinVar as [Benign]. Clinvar id is 65253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2086623-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.4850-109T>C		intron_variant		ENST00000219476.9	NP_000539.2	P49815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.4850-109T>C		intron_variant		5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41725

AN:

151976

Hom.:

7964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.177

AC:

244845

AN:

1385990

Hom.:

25022

AF XY:

0.173

AC XY:

118993

AN XY:

686782

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.000241

Gnomad4 SAS exome

AF:

0.0962

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.275

AC:

41810

AN:

152094

Hom.:

8001

Cov.:

AF XY:

0.272

AC XY:

20214

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.541

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0925

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.157

Hom.:

478

Bravo

AF:

0.284

Asia WGS

AF:

0.0830

AC:

291

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 21. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Tuberous sclerosis syndrome

Other:1

not provided, no classification provided

curation

Tuberous sclerosis database (TSC2)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.82

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over