Variant 16-2062649-CTCTG-C 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.1361+54_1361+57del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,547,758 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 16 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Not classified

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.398

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0024 (365/152348) while in subpopulation NFE AF= 0.00393 (267/68022). AF 95% confidence interval is 0.00354. There are 0 homozygotes in gnomad4. There are 165 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 365 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.1361+54_1361+57del		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.1361+54_1361+57del		intron_variant		5	NM_000548.5		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

365

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00392

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00229

AC:

404

AN:

176058

Hom.:

AF XY:

0.00223

AC XY:

210

AN XY:

94042

show subpopulations

Gnomad AFR exome

AF:

0.000673

Gnomad AMR exome

AF:

0.00303

Gnomad ASJ exome

AF:

0.000451

Gnomad EAS exome

AF:

0.0000750

Gnomad SAS exome

AF:

0.000329

Gnomad FIN exome

AF:

0.000242

Gnomad NFE exome

AF:

0.00394

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00380

AC:

5297

AN:

1395410

Hom.:

AF XY:

0.00366

AC XY:

2531

AN XY:

690820

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.000316

Gnomad4 EAS exome

AF:

0.0000537

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00458

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00240

AC:

365

AN:

152348

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

165

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.00282

Asia WGS

AF:

0.000289

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)

0.0

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