NM_000548.5:c.2601T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_000548.5(TSC2):c.2601T>C(p.Ser867Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TSC2
NM_000548.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.67

Publications

0 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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 16-2075854-T-C is Benign according to our data. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2075854-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 237998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC2	NM_000548.5 link	c.2601T>C	p.Ser867Ser	synonymous_variant	Exon 23 of 42	ENST00000219476.9	NP_000539.2	P49815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 link	c.2601T>C	p.Ser867Ser	synonymous_variant	Exon 23 of 42	5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Tuberous sclerosis 2

Benign:3

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 20, 2025

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Oct 20, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 20, 2018

GeneDx

Significance:Likely 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. -

Hereditary cancer-predisposing syndrome

Benign:1

Jul 12, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.16

(source)

DANN

Benign

0.48

PhyloP100

-1.7

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over