NM_000548.5(TSC2):c.138+5G>A AND Tuberous sclerosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 10, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001380069.5

Allele description [Variation Report for NM_000548.5(TSC2):c.138+5G>A]

NM_000548.5(TSC2):c.138+5G>A

Gene:

TSC2:TSC complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000548.5(TSC2):c.138+5G>A

HGVS:

NC_000016.10:g.2048758G>A
NG_005895.1:g.4453G>A
NG_008412.1:g.4109C>T
NM_000548.5:c.138+5G>AMANE SELECT
NM_001077183.3:c.138+5G>A
NM_001114382.3:c.138+5G>A
NM_001318827.2:c.138+5G>A
NM_001318829.2:c.-10+693G>A
NM_001318831.2:c.-89+5G>A
NM_001318832.2:c.171+5G>A
NM_001363528.2:c.138+5G>A
NM_001370404.1:c.138+5G>A
NM_001370405.1:c.138+5G>A
NM_021055.3:c.138+5G>A
LRG_487t1:c.138+5G>A
LRG_1366:g.4109C>T
LRG_487:g.4453G>A
NC_000016.9:g.2098759G>A
NM_000548.3:c.138+5G>A
p.?

Links:

Tuberous sclerosis database (TSC2): TSC2_00034; dbSNP: rs45481400

NCBI 1000 Genomes Browser:

rs45481400

Molecular consequence:

NM_000548.5:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001077183.3:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001114382.3:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001318827.2:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001318829.2:c.-10+693G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001318831.2:c.-89+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001318832.2:c.171+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001363528.2:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001370404.1:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001370405.1:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_021055.3:c.138+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Tuberous sclerosis 2 (TSC2)
Identifiers:: MONDO: MONDO:0013199; MedGen: C1860707; Orphanet: 805; OMIM: 613254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001578011	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 10, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10735580, 11112665, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001578011

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 10, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Superiority of denaturing high performance liquid chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2.

Choy YS, Dabora SL, Hall F, Ramesh V, Niida Y, Franz D, Kasprzyk-Obara J, Reeve MP, Kwiatkowski DJ.

Ann Hum Genet. 1999 Sep;63(Pt 5):383-91.

PubMed [citation]

PMID:: 10735580

Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ.

Am J Hum Genet. 2001 Jan;68(1):64-80. Epub 2000 Dec 8.

PubMed [citation]

PMID:: 11112665
PMCID:: PMC1234935

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001578011.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has been observed in individual(s) with clinical features of tuberous sclerosis (PMID: 10735580, 11112665). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 50192). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This sequence change falls in intron 2 of the TSC2 gene. It does not directly change the encoded amino acid sequence of the TSC2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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