Variant chr16-2085072-C-T 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.4569+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,610,540 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 34)

Exomes 𝑓: 0.014 ( 169 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.450

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=-0.88).

BP6

Variant 16-2085072-C-T is Benign according to our data. Variant chr16-2085072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 49857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2085072-C-T is described in Lovd as [Benign]. Variant chr16-2085072-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1595/152328) while in subpopulation NFE AF= 0.0187 (1270/68024). AF 95% confidence interval is 0.0178. There are 14 homozygotes in gnomad4. There are 726 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1595 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.4569+46C>T		intron_variant		ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.4569+46C>T		intron_variant		5	NM_000548.5	ENSP00000219476		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1595

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0103

AC:

2564

AN:

249256

Hom.:

AF XY:

0.0102

AC XY:

1379

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.00255

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00714

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0139

AC:

20268

AN:

1458212

Hom.:

169

Cov.:

AF XY:

0.0137

AC XY:

9910

AN XY:

725618

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00355

Gnomad4 FIN exome

AF:

0.00760

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0105

AC:

1595

AN:

152328

Hom.:

Cov.:

AF XY:

0.00975

AC XY:

726

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0187

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00958

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Tuberous sclerosis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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

-0.88

CADD

Benign

0.76

DANN

Benign

0.36

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