Variant 16-2083900-C-T 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.4005+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,518,862 control chromosomes in the GnomAD database, including 6,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 435 hom., cov: 34)

Exomes 𝑓: 0.088 ( 5723 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.184

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=-0.88).

BP6

Variant 16-2083900-C-T is Benign according to our data. Variant chr16-2083900-C-T is described in ClinVar as [Benign]. Clinvar id is 1266887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0926 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.4005+84C>T		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.4005+84C>T		intron_variant		5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9725

AN:

152102

Hom.:

435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0539

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0370

Gnomad SAS

AF:

0.0505

Gnomad FIN

AF:

0.0763

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0945

Gnomad OTH

AF:

0.0641

GnomAD4 exome

AF:

0.0878

AC:

120006

AN:

1366642

Hom.:

5723

AF XY:

0.0873

AC XY:

58626

AN XY:

671510

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.0372

Gnomad4 ASJ exome

AF:

0.0737

Gnomad4 EAS exome

AF:

0.0538

Gnomad4 SAS exome

AF:

0.0504

Gnomad4 FIN exome

AF:

0.0863

Gnomad4 NFE exome

AF:

0.0961

Gnomad4 OTH exome

AF:

0.0816

GnomAD4 genome

AF:

0.0638

AC:

9717

AN:

152220

Hom.:

435

Cov.:

AF XY:

0.0633

AC XY:

4710

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0538

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.0369

Gnomad4 SAS

AF:

0.0499

Gnomad4 FIN

AF:

0.0763

Gnomad4 NFE

AF:

0.0945

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0853

Hom.:

400

Bravo

AF:

0.0581

Asia WGS

AF:

0.0390

AC:

134

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

DANN

Benign

0.36

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