NM_000548.5:c.3883+8C>G

Variant names:

• chr16-2082512-C-G
• rs45517316
• NM_000548.5:c.3883+8C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000548.5(TSC2):​c.3883+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,610,876 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 34)
  • Exomes 𝑓: 0.0012 (36 hom.)
• Consequence: TSC2 NM_000548.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001776
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17 O:1
• Conservation: PhyloP100: 0.709
• Publications: 3 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: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, 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=-0.79).
• BP6: Variant 16-2082512-C-G is Benign according to our data. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2082512-C-G is described in CliVar as Benign/Likely_benign. Clinvar id is 50027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1818/152348) while in subpopulation AFR AF = 0.0417 (1732/41580). AF 95% confidence interval is 0.04. There are 32 homozygotes in GnomAd4. There are 908 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC2	NM_000548.5	c.3883+8C>G		splice_region_variant, intron_variant	Intron 32 of 41	ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9	c.3883+8C>G		splice_region_variant, intron_variant	Intron 32 of 41	5	NM_000548.5	ENSP00000219476.3

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1816 AN: 152230 Hom.: 32 Cov.: 34

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

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: 0.000103

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00299 AC: 744 AN: 248470 AF XY: 0.00224

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00123 AC: 1795 AN: 1458528 Hom.: 36 Cov.: 31 AF XY: 0.00105 AC XY: 765 AN XY: 725664

African (AFR) AF: 0.0429 AC: 1435 AN: 33480

American (AMR) AF: 0.00295 AC: 132 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50238

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111902

Other (OTH) AF: 0.00293 AC: 177 AN: 60356

GnomAD4 genome AF: 0.0119 AC: 1818 AN: 152348 Hom.: 32 Cov.: 34 AF XY: 0.0122 AC XY: 908 AN XY: 74492

African (AFR) AF: 0.0417 AC: 1732 AN: 41580

American (AMR) AF: 0.00385 AC: 59 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00503 Hom.: 4

Bravo AF: 0.0134

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:17 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Jan 14, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 05, 2018

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: TSC2 c.3883+8C>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0039 in 274946 control chromosomes in the gnomAD database, including 24 homozygotes. The observed variant frequency is approximately 57-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3883+8C>G in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign. -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tuberous sclerosis 2 Benign:4

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 02, 2025

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:4

Jan 25, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 04, 2023

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Tuberous sclerosis syndrome Benign:2 Other:1

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Tuberous sclerosis database (TSC2)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 23, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lymphangiomyomatosis;C1846385:Isolated focal cortical dysplasia type II;C1860707:Tuberous sclerosis 2 Benign:1

Jul 23, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.71
PromoterAI		0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.060		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: rs45517316; hg19: chr16-2132513; COSMIC: COSV105872708; COSMIC: COSV105872708;