Variant rs1800705 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000548.5(TSC2):c.3883+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,512,880 control chromosomes in the GnomAD database, including 1,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 104 hom., cov: 34)

Exomes 𝑓: 0.036 ( 1007 hom. )

Consequence

TSC2
NM_000548.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0180

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-2082582-G-A is Benign according to our data. Variant chr16-2082582-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 49278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082582-G-A is described in Lovd as [Benign]. Variant chr16-2082582-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4011/152318) while in subpopulation NFE AF= 0.0403 (2738/68020). AF 95% confidence interval is 0.039. There are 104 homozygotes in gnomad4. There are 1845 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4011 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5 linkuse as main transcript	c.3883+78G>A		intron_variant		ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9 linkuse as main transcript	c.3883+78G>A		intron_variant		5	NM_000548.5	ENSP00000219476		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4012

AN:

152200

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00709

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0359

GnomAD4 exome

AF:

0.0356

AC:

48502

AN:

1360562

Hom.:

1007

Cov.:

AF XY:

0.0350

AC XY:

23869

AN XY:

681906

show subpopulations

Gnomad4 AFR exome

AF:

0.00550

Gnomad4 AMR exome

AF:

0.0224

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0315

GnomAD4 genome

AF:

0.0263

AC:

4011

AN:

152318

Hom.:

104

Cov.:

AF XY:

0.0248

AC XY:

1845

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00707

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.0403

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0304

Hom.:

Bravo

AF:

0.0276

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 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. -

Tuberous sclerosis syndrome

Other:1

not provided, no classification provided

curation

Tuberous sclerosis database (TSC2)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over