Variant 16-2060570-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.976-100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,595,738 control chromosomes in the GnomAD database, including 257,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22385 hom., cov: 31)

Exomes 𝑓: 0.57 ( 234848 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.93

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=-0.92).

BP6

Variant 16-2060570-C-G is Benign according to our data. Variant chr16-2060570-C-G is described in ClinVar as [Benign]. Clinvar id is 675047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2060570-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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.976-100C>G		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.976-100C>G		intron_variant		5	NM_000548.5		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81643

AN:

151816

Hom.:

22360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.548

GnomAD4 exome

AF:

0.568

AC:

820770

AN:

1443804

Hom.:

234848

AF XY:

0.572

AC XY:

411257

AN XY:

718734

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.600

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.649

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.575

GnomAD4 genome

AF:

0.538

AC:

81701

AN:

151934

Hom.:

22385

Cov.:

AF XY:

0.539

AC XY:

39990

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.713

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.444

Hom.:

1312

Bravo

AF:

0.526

Asia WGS

AF:

0.699

AC:

2429

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 43. Only high quality variants are reported. -

Tuberous sclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.15

DANN

Benign

0.45

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