Variant 16-2076451-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000548.5(TSC2):c.2743-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 1,611,124 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 94 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.789

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=-0.85).

BP6

Variant 16-2076451-A-G is Benign according to our data. Variant chr16-2076451-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 49756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2076451-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00601 (913/151998) while in subpopulation NFE AF= 0.00969 (658/67934). AF 95% confidence interval is 0.00907. There are 3 homozygotes in gnomad4. There are 390 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 913 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.2743-40A>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.2743-40A>G		intron_variant		5	NM_000548.5		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

913

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00499

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00968

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00715

AC:

1787

AN:

249768

Hom.:

AF XY:

0.00761

AC XY:

1031

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00677

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00706

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.00914

AC:

13338

AN:

1459126

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

6708

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.00696

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00731

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00894

GnomAD4 genome

AF:

0.00601

AC:

913

AN:

151998

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

390

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00499

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00969

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00728

Hom.:

Bravo

AF:

0.00680

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 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

-0.85

CADD

Benign

1.1

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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