rs587778009

chr16-2053837-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000548.5(TSC2):c.336+385C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 498,826 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 not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.713

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC2	NM_000548.5	c.336+385C>G		intron_variant		ENST00000219476.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC2	ENST00000219476.9	c.336+385C>G		intron_variant		5	NM_000548.5

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000797 AC: 10 AN: 125440 Hom.: 0 AF XY: 0.0000729 AC XY: 5 AN XY: 68576

Gnomad AFR exome AF: 0.000165

Gnomad AMR exome AF: 0.0000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.000256

GnomAD4 exome AF: 0.000133 AC: 46 AN: 346620 Hom.: 0 Cov.: 0 AF XY: 0.000129 AC XY: 25 AN XY: 193078

Gnomad4 AFR exome AF: 0.0000949

Gnomad4 AMR exome AF: 0.0000706

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.000228

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74346

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000170

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.50
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs587778009; hg19: chr16-2103838;