Variant 16-2075936-C-G 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.2639+44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,368 control chromosomes in the GnomAD database, including 17,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 6778 hom., cov: 33)

Exomes 𝑓: 0.094 ( 10713 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.683

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-2075936-C-G is Benign according to our data. Variant chr16-2075936-C-G is described in ClinVar as [Benign]. Clinvar id is 50084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075936-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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.2639+44C>G		intron_variant		ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.2639+44C>G		intron_variant		5	NM_000548.5	ENSP00000219476		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32423

AN:

152140

Hom.:

6741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0812

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.107

AC:

26715

AN:

249504

Hom.:

3286

AF XY:

0.0983

AC XY:

13316

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.0695

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0636

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.0846

Gnomad OTH exome

AF:

0.0950

GnomAD4 exome

AF:

0.0935

AC:

136523

AN:

1460110

Hom.:

10713

Cov.:

AF XY:

0.0907

AC XY:

65924

AN XY:

726460

show subpopulations

Gnomad4 AFR exome

AF:

0.565

Gnomad4 AMR exome

AF:

0.0746

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.0834

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.214

AC:

32509

AN:

152258

Hom.:

6778

Cov.:

AF XY:

0.211

AC XY:

15686

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0619

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0812

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.0621

Hom.:

108

Bravo

AF:

0.228

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Tuberous sclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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

-0.91

CADD

Benign

0.83

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