16-2062962-C-T

Variant names:

• chr16-2062962-C-T
• rs45446697
• NM_000548.5:c.1362-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000548.5(TSC2):​c.1362-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,549,312 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 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Scores: Splicing: ADA: 0.00001193
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.133
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-2062962-C-T is Benign according to our data. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2062962-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 389376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000229 (32/1397076) while in subpopulation AFR AF = 0.00057 (18/31560). AF 95% confidence interval is 0.000368. There are 0 homozygotes in GnomAdExome4. There are 17 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC2	NM_000548.5	c.1362-10C>T		intron_variant	Intron 13 of 41	ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9	c.1362-10C>T		intron_variant	Intron 13 of 41	5	NM_000548.5	ENSP00000219476.3

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000259 AC: 4 AN: 154196 AF XY: 0.0000246

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000229 AC: 32 AN: 1397076 Hom.: 0 Cov.: 31 AF XY: 0.0000247 AC XY: 17 AN XY: 689098

African (AFR) AF: 0.000570 AC: 18 AN: 31560

American (AMR) AF: 0.0000280 AC: 1 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25154

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35724

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5082

European-Non Finnish (NFE) AF: 0.00000464 AC: 5 AN: 1078698

Other (OTH) AF: 0.000104 AC: 6 AN: 57882

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74368

African (AFR) AF: 0.000386 AC: 16 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000193

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tuberous sclerosis 2 Benign:3

Sep 05, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tuberous sclerosis syndrome Benign:1

Nov 08, 2022

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Sep 10, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Feb 23, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		-0.13
PromoterAI		-0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs45446697; hg19: chr16-2112963;