rs1800715

Variant names:

• chr16-2075936-C-G
• rs1800715
• NM_000548.5:c.2639+44C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2075936-C-G
• chr16-2075936-C-A
• chr16-2075936-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000548.5(TSC2):​c.2639+44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,368 control chromosomes in the GnomAD database, including 17,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (6778 hom., cov: 33)
  • Exomes 𝑓: 0.094 (10713 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: 0.683
• Publications: 10 publications found

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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• lymphangioleiomyomatosis

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• tuberous sclerosis complex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-2075936-C-G is Benign according to our data. Variant chr16-2075936-C-G is described in ClinVar as Benign. ClinVar VariationId is 50084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSC2	NM_000548.5	MANE Select	c.2639+44C>G		intron	N/A	NP_000539.2	P49815-1
	TSC2	NM_001406663.1		c.2639+44C>G		intron	N/A	NP_001393592.1	A0A2R8Y6C9
	TSC2	NM_001114382.3		c.2639+44C>G		intron	N/A	NP_001107854.1	P49815-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSC2	ENST00000219476.9	TSL:5 MANE Select	c.2639+44C>G		intron	N/A	ENSP00000219476.3	P49815-1
	TSC2	ENST00000350773.9	TSL:1	c.2639+44C>G		intron	N/A	ENSP00000344383.4	P49815-4
	TSC2	ENST00000401874.7	TSL:1	c.2639+44C>G		intron	N/A	ENSP00000384468.2	P49815-5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32423 AN: 152140 Hom.: 6741 Cov.: 33

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.107 AC: 26715 AN: 249504 AF XY: 0.0983

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.0695

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0846

Gnomad OTH exome AF: 0.0950

GnomAD4 exome AF: 0.0935 AC: 136523 AN: 1460110 Hom.: 10713 Cov.: 32 AF XY: 0.0907 AC XY: 65924 AN XY: 726460

African (AFR) AF: 0.565 AC: 18912 AN: 33462

American (AMR) AF: 0.0746 AC: 3335 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2716 AN: 26116

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39686

South Asian (SAS) AF: 0.0641 AC: 5530 AN: 86236

European-Finnish (FIN) AF: 0.112 AC: 5872 AN: 52312

Middle Eastern (MID) AF: 0.118 AC: 679 AN: 5764

European-Non Finnish (NFE) AF: 0.0834 AC: 92738 AN: 1111468

Other (OTH) AF: 0.112 AC: 6733 AN: 60366

GnomAD4 genome AF: 0.214 AC: 32509 AN: 152258 Hom.: 6778 Cov.: 33 AF XY: 0.211 AC XY: 15686 AN XY: 74450

African (AFR) AF: 0.547 AC: 22724 AN: 41512

American (AMR) AF: 0.129 AC: 1973 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0619 AC: 299 AN: 4832

European-Finnish (FIN) AF: 0.110 AC: 1171 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0812 AC: 5523 AN: 68032

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.0621 Hom.: 108

Bravo AF: 0.228

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Tuberous sclerosis 2 (1)
-	-	-	Tuberous sclerosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.43
PhyloP100		0.68
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800715; hg19: chr16-2125937; COSMIC: COSV54756601; COSMIC: COSV54756601;