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NM_000548.5(TSC2):c.5161-2A>G AND Tuberous sclerosis 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 6, 2022
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:
RCV002526065.3

Allele description [Variation Report for NM_000548.5(TSC2):c.5161-2A>G]

NM_000548.5(TSC2):c.5161-2A>G

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.5161-2A>G
HGVS:
  • NC_000016.10:g.2088225A>G
  • NG_005895.1:g.43920A>G
  • NG_008617.1:g.54996T>C
  • NM_000548.5:c.5161-2A>GMANE SELECT
  • NM_001077183.3:c.4960-2A>G
  • NM_001114382.3:c.5092-2A>G
  • NM_001318827.2:c.4852-2A>G
  • NM_001318829.2:c.4816-2A>G
  • NM_001318831.2:c.4429-2A>G
  • NM_001318832.2:c.4993-2A>G
  • NM_001363528.2:c.4963-2A>G
  • NM_001370404.1:c.5029-2A>G
  • NM_001370405.1:c.5032-14A>G
  • NM_001406663.1:c.5158-2A>G
  • NM_001406664.1:c.5089-2A>G
  • NM_001406665.1:c.5083-2A>G
  • NM_001406667.1:c.5053-2A>G
  • NM_001406668.1:c.5050-2A>G
  • NM_001406670.1:c.4981-2A>G
  • NM_001406671.1:c.4951-2A>G
  • NM_001406673.1:c.4948-2A>G
  • NM_001406675.1:c.4945-2A>G
  • NM_001406676.1:c.4942-2A>G
  • NM_001406677.1:c.4903-2A>G
  • NM_001406678.1:c.4849-2A>G
  • NM_001406679.1:c.4813-2A>G
  • NM_001406680.1:c.4561-2A>G
  • NM_001406681.1:c.4501-2A>G
  • NM_001406682.1:c.4492-2A>G
  • NM_001406683.1:c.4492-2A>G
  • NM_001406684.1:c.4489-2A>G
  • NM_001406685.1:c.4363-2A>G
  • NM_001406686.1:c.4363-2A>G
  • NM_001406687.1:c.4360-2A>G
  • NM_001406688.1:c.4360-2A>G
  • NM_001406689.1:c.3748-2A>G
  • NM_001406690.1:c.3688-2A>G
  • NM_001406691.1:c.3685-2A>G
  • NM_001406692.1:c.3619-2A>G
  • NM_001406693.1:c.3619-2A>G
  • NM_001406694.1:c.3619-2A>G
  • NM_001406695.1:c.3616-2A>G
  • NM_001406696.1:c.3616-2A>G
  • NM_001406697.1:c.3616-2A>G
  • NM_001406698.1:c.3358-2A>G
  • NM_021055.3:c.5032-2A>G
  • LRG_487t1:c.5161-2A>G
  • LRG_487:g.43920A>G
  • NC_000016.9:g.2138226A>G
  • NM_000548.3:c.5161-2A>G
Links:
dbSNP: rs1114167468
NCBI 1000 Genomes Browser:
rs1114167468
Molecular consequence:
  • NM_001370405.1:c.5032-14A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000548.5:c.5161-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001077183.3:c.4960-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001114382.3:c.5092-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318827.2:c.4852-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318829.2:c.4816-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318831.2:c.4429-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001318832.2:c.4993-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363528.2:c.4963-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001370404.1:c.5029-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406663.1:c.5158-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406664.1:c.5089-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406665.1:c.5083-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406667.1:c.5053-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406668.1:c.5050-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406670.1:c.4981-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406671.1:c.4951-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406673.1:c.4948-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406675.1:c.4945-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406676.1:c.4942-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406677.1:c.4903-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406678.1:c.4849-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406679.1:c.4813-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406680.1:c.4561-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406681.1:c.4501-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406682.1:c.4492-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406683.1:c.4492-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406684.1:c.4489-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406685.1:c.4363-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406686.1:c.4363-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406687.1:c.4360-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406688.1:c.4360-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406689.1:c.3748-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406690.1:c.3688-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406691.1:c.3685-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406692.1:c.3619-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406693.1:c.3619-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406694.1:c.3619-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406695.1:c.3616-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406696.1:c.3616-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406697.1:c.3616-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406698.1:c.3358-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_021055.3:c.5032-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003461707Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 6, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Deep phenotyping of patients with Tuberous Sclerosis Complex and no mutation identified in TSC1 and TSC2.

Peron A, Vignoli A, Briola F, Morenghi E, Tansini L, Alfano RM, Bulfamante G, Terraneo S, Ghelma F, Banderali G, Viskochil DH, Carey JC, Canevini MP; TSC Study Group of the San Paolo Hospital of Milan..

Eur J Med Genet. 2018 Jul;61(7):403-410. doi: 10.1016/j.ejmg.2018.02.005. Epub 2018 Feb 9.

PubMed [citation]
PMID:
29432982

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

Bullich G, Domingo-Gallego A, Vargas I, Ruiz P, Lorente-Grandoso L, Furlano M, Fraga G, Madrid Á, Ariceta G, Borregán M, Piñero-Fernández JA, Rodríguez-Peña L, Ballesta-Martínez MJ, Llano-Rivas I, Meñica MA, Ballarín J, Torrents D, Torra R, Ars E.

Kidney Int. 2018 Aug;94(2):363-371. doi: 10.1016/j.kint.2018.02.027. Epub 2018 May 22.

PubMed [citation]
PMID:
29801666
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003461707.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 427999). Disruption of this splice site has been observed in individuals with clinical features of tuberous sclerosis complex (PMID: 29432982, 29801666). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 40 of the TSC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024