chr16-2065818-A-G

Position:

• chr16-2065818-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000548.5(TSC2):​c.1716+183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,016 control chromosomes in the GnomAD database, including 25,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (25506 hom., cov: 31)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.448

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-2065818-A-G is Benign according to our data. Variant chr16-2065818-A-G is described in ClinVar as [Benign]. Clinvar id is 677145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.1716+183A>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.1716+183A>G		intron_variant		5	NM_000548.5	ENSP00000219476

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86064 AN: 151898 Hom.: 25476 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 86119 AN: 152016 Hom.: 25506 Cov.: 31 AF XY: 0.571 AC XY: 42396 AN XY: 74308

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.583

Alfa AF: 0.595 Hom.: 13417

Bravo AF: 0.564

Asia WGS AF: 0.763 AC: 2649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.39
DANN	Benign	0.52

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: rs8063461; hg19: chr16-2115819; COSMIC: COSV104375716; COSMIC: COSV104375716;