Variant 16-2072390-TGG-TG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_000548.5(TSC2):c.2220+32delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,612,866 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 19 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Not classified

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -3.26

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0028 (426/152168) while in subpopulation SAS AF= 0.00953 (46/4826). AF 95% confidence interval is 0.00734. There are 2 homozygotes in gnomad4. There are 227 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 426 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.2220+32delG		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.2220+32delG		intron_variant		5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

426

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00867

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00350

AC:

874

AN:

249924

Hom.:

AF XY:

0.00394

AC XY:

533

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00648

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00918

Gnomad FIN exome

AF:

0.00210

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00344

AC:

5026

AN:

1460698

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

2705

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00839

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00958

Gnomad4 FIN exome

AF:

0.00181

Gnomad4 NFE exome

AF:

0.00308

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.00280

AC:

426

AN:

152168

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00867

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00330

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00281

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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