rs7187438

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000548.5(TSC2):c.1717-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,612,486 control chromosomes in the GnomAD database, including 103,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15472 hom., cov: 33)

Exomes 𝑓: 0.34 ( 88204 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.572

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-2070401-T-C is Benign according to our data. Variant chr16-2070401-T-C is described in ClinVar as Benign. ClinVar VariationId is 65157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC2	NM_000548.5 link	c.1717-55T>C		intron_variant	Intron 16 of 41	ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 link	c.1717-55T>C		intron_variant	Intron 16 of 41	5	NM_000548.5	ENSP00000219476.3

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64283

AN:

151948

Hom.:

15446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.440

GnomAD4 exome

AF:

0.341

AC:

497687

AN:

1460420

Hom.:

88204

AF XY:

0.338

AC XY:

245381

AN XY:

726492

show subpopulations

African (AFR)

AF:

0.693

AC:

23209

AN:

33472

American (AMR)

AF:

0.225

AC:

10074

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

10340

AN:

26130

East Asian (EAS)

AF:

0.263

AC:

10445

AN:

39688

South Asian (SAS)

AF:

0.265

AC:

22823

AN:

86238

European-Finnish (FIN)

AF:

0.288

AC:

15078

AN:

52276

Middle Eastern (MID)

AF:

0.441

AC:

2544

AN:

5764

European-Non Finnish (NFE)

AF:

0.343

AC:

381330

AN:

1111800

Other (OTH)

AF:

0.362

AC:

21844

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

21878

43756

65634

87512

109390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12208

24416

36624

48832

61040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.423

AC:

64348

AN:

152066

Hom.:

15472

Cov.:

AF XY:

0.417

AC XY:

31016

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.672

AC:

27849

AN:

41450

American (AMR)

AF:

0.325

AC:

4962

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1364

AN:

3468

East Asian (EAS)

AF:

0.237

AC:

1228

AN:

5180

South Asian (SAS)

AF:

0.254

AC:

1226

AN:

4822

European-Finnish (FIN)

AF:

0.298

AC:

3158

AN:

10588

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23095

AN:

67956

Other (OTH)

AF:

0.435

AC:

919

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1785

3570

5354

7139

8924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.379

Hom.:

16788

Bravo

AF:

0.442

Asia WGS

AF:

0.255

AC:

888

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 40. Only high quality variants are reported. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Tuberous sclerosis 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tuberous sclerosis syndrome

Other:1

Tuberous sclerosis database (TSC2)

Significance:not provided

Review Status:no classification provided

Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.27

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over