rs772993105

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000548.5(TSC2):c.2019G>A(p.Ala673Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,405,554 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A673A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TSC2
NM_000548.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-2071856-G-A is Benign according to our data. Variant chr16-2071856-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 388343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAdExome4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000548.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSC2	NM_000548.5	MANE Select	c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 42	NP_000539.2	P49815-1
TSC2	NM_001406663.1		c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 42	NP_001393592.1	A0A2R8Y6C9
TSC2	NM_001114382.3		c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 41	NP_001107854.1	P49815-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSC2	ENST00000219476.9	TSL:5 MANE Select	c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 42	ENSP00000219476.3	P49815-1
TSC2	ENST00000350773.9	TSL:1	c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 41	ENSP00000344383.4	P49815-4
TSC2	ENST00000401874.7	TSL:1	c.2019G>A	p.Ala673Ala	synonymous	Exon 19 of 40	ENSP00000384468.2	P49815-5

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

157298

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1405554

Hom.:

Cov.:

AF XY:

0.00000720

AC XY:

AN XY:

694924

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32102

American (AMR)

AF:

0.00

AC:

AN:

38146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24968

East Asian (EAS)

AF:

0.00

AC:

AN:

36920

South Asian (SAS)

AF:

0.0000754

AC:

AN:

79620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4378

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1085006

Other (OTH)

AF:

0.0000172

AC:

AN:

58084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000136

AC:

AN:

147178

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71390

show subpopulations

African (AFR)

AF:

0.0000256

AC:

AN:

39030

American (AMR)

AF:

0.00

AC:

AN:

14846

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5008

South Asian (SAS)

AF:

0.00

AC:

AN:

4630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67316

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Tuberous sclerosis 2 (3)

Hereditary cancer-predisposing syndrome (1)

not provided (1)

Tuberous sclerosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.25

(source)

DANN

Benign

0.54

PhyloP100

-4.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over