Variant rs137854220 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000548.5(TSC2):c.5161-28_5161-25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,612,902 control chromosomes in the GnomAD database, including 128 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 10 hom., cov: 33)

Exomes 𝑓: 0.010 ( 118 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1O:2

Conservation

PhyloP100: 2.09

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 -10 ACMG points.

BP6

Variant 16-2088196-TAGTG-T is Benign according to our data. Variant chr16-2088196-TAGTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 49945.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-2088196-TAGTG-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00824 (1255/152226) while in subpopulation SAS AF= 0.0141 (68/4832). AF 95% confidence interval is 0.0115. There are 10 homozygotes in gnomad4. There are 591 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.5161-28_5161-25del		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.5161-28_5161-25del		intron_variant		5	NM_000548.5		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.00827

AC:

1258

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00860

AC:

2155

AN:

250500

Hom.:

AF XY:

0.00922

AC XY:

1252

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00738

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.00513

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00850

GnomAD4 exome

AF:

0.0103

AC:

15017

AN:

1460676

Hom.:

118

AF XY:

0.0106

AC XY:

7718

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.00639

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.00529

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00880

GnomAD4 genome

AF:

0.00824

AC:

1255

AN:

152226

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

591

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00751

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tuberous sclerosis syndrome

Other:2

not provided, no classification provided	curation	Tuberous sclerosis database (TSC2)	Apr 06, 2011	- -
not provided, no classification provided	curation	Tuberous sclerosis database (TSC2)	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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