rs796053477

chr16-2086173-CCT-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_000548.5(TSC2):c.4663-16_4663-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,612,172 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.817

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 16-2086173-CCT-C is Benign according to our data. Variant chr16-2086173-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 207688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2086173-CCT-C is described in Lovd as [Benign].
• BS2: High AC in GnomAd at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5	c.4663-16_4663-15del		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9	c.4663-16_4663-15del		intron_variant		5	NM_000548.5

Frequencies

GnomAD3 genomes AF: 0.000500 AC: 76 AN: 152064 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000411 AC: 102 AN: 248074 Hom.: 0 AF XY: 0.000378 AC XY: 51 AN XY: 134996

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00532

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000229 AC: 335 AN: 1459990 Hom.: 1 AF XY: 0.000249 AC XY: 181 AN XY: 726324

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.00709

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000486

Gnomad4 OTH exome AF: 0.000878

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.000484 AC XY: 36 AN XY: 74396

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000712 Hom.: 0

Bravo AF: 0.000839

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2014	The variant is found in EPILEPSY panel(s). -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Tuberous sclerosis 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs796053477; hg19: chr16-2136174;