Variant rs45517351 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000548.5(TSC2):c.4569+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,610,572 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 70 hom., cov: 34)

Exomes 𝑓: 0.0020 ( 66 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -1.19

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 -16 ACMG points.

BP6

Variant 16-2085073-G-A is Benign according to our data. Variant chr16-2085073-G-A is described in ClinVar as [Benign]. Clinvar id is 49858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2085073-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.4569+47G>A		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.4569+47G>A		intron_variant		5	NM_000548.5		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2605

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00778

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00473

AC:

1179

AN:

249126

Hom.:

AF XY:

0.00347

AC XY:

470

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00542

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000312

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00199

AC:

2897

AN:

1458266

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1279

AN XY:

725600

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00705

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00468

GnomAD4 genome

AF:

0.0172

AC:

2618

AN:

152306

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1271

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0585

Gnomad4 AMR

AF:

0.00777

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00208

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Tuberous sclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

-0.89

Cadd

Benign

0.10

Dann

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: 1

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