16-2055054-A-G

Position:

• chr16-2055054-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000548.5(TSC2):​c.482-348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 403,308 control chromosomes in the GnomAD database, including 87,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (36202 hom., cov: 31)
  • Exomes 𝑓: 0.64 (51730 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.482-348A>G		intron_variant		ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9	c.482-348A>G		intron_variant		5	NM_000548.5	ENSP00000219476.3

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103695 AN: 151842 Hom.: 36139 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.665

GnomAD4 exome AF: 0.638 AC: 160320 AN: 251348 Hom.: 51730 Cov.: 0 AF XY: 0.644 AC XY: 86370 AN XY: 134204

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.778

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.633

GnomAD4 genome AF: 0.683 AC: 103814 AN: 151960 Hom.: 36202 Cov.: 31 AF XY: 0.680 AC XY: 50531 AN XY: 74266

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.669

Alfa AF: 0.616 Hom.: 37055

Bravo AF: 0.693

Asia WGS AF: 0.775 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.28
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: rs2073636; hg19: chr16-2105055;