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NM_000548.5(TSC2):c.1257+2T>C AND Tuberous sclerosis 2

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 6, 2023
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:
RCV000722173.5

Allele description [Variation Report for NM_000548.5(TSC2):c.1257+2T>C]

NM_000548.5(TSC2):c.1257+2T>C

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.1257+2T>C
HGVS:
  • NC_000016.10:g.2062010T>C
  • NG_005895.1:g.17705T>C
  • NM_000548.5:c.1257+2T>CMANE SELECT
  • NM_001077183.3:c.1257+2T>C
  • NM_001114382.3:c.1257+2T>C
  • NM_001318827.2:c.1146+2T>C
  • NM_001318829.2:c.1110+2T>C
  • NM_001318831.2:c.657+2T>C
  • NM_001318832.2:c.1290+2T>C
  • NM_001363528.2:c.1257+2T>C
  • NM_001370404.1:c.1257+2T>C
  • NM_001370405.1:c.1257+2T>C
  • NM_001406663.1:c.1257+2T>C
  • NM_001406664.1:c.1257+2T>C
  • NM_001406665.1:c.1257+2T>C
  • NM_001406667.1:c.1347+2T>C
  • NM_001406668.1:c.1347+2T>C
  • NM_001406670.1:c.1146+2T>C
  • NM_001406671.1:c.1245+2T>C
  • NM_001406673.1:c.1245+2T>C
  • NM_001406675.1:c.1110+2T>C
  • NM_001406676.1:c.1110+2T>C
  • NM_001406677.1:c.1200+2T>C
  • NM_001406678.1:c.1146+2T>C
  • NM_001406679.1:c.1110+2T>C
  • NM_001406680.1:c.657+2T>C
  • NM_001406681.1:c.795+2T>C
  • NM_001406682.1:c.657+2T>C
  • NM_001406683.1:c.657+2T>C
  • NM_001406684.1:c.657+2T>C
  • NM_001406685.1:c.657+2T>C
  • NM_001406686.1:c.657+2T>C
  • NM_001406687.1:c.657+2T>C
  • NM_001406688.1:c.657+2T>C
  • NM_001406689.1:c.-88+2T>C
  • NM_001406690.1:c.-88+2T>C
  • NM_001406691.1:c.-88+2T>C
  • NM_001406692.1:c.-88+2T>C
  • NM_001406693.1:c.-88+2T>C
  • NM_001406694.1:c.-56+2T>C
  • NM_001406695.1:c.-56+2T>C
  • NM_001406696.1:c.-88+2T>C
  • NM_001406697.1:c.-88+2T>C
  • NM_001406698.1:c.-264+2T>C
  • NM_021055.3:c.1257+2T>C
  • LRG_487t1:c.1257+2T>C
  • LRG_487:g.17705T>C
  • NC_000016.9:g.2112011T>C
  • NM_000548.3:c.1257+2T>C
  • p.?
Links:
Tuberous sclerosis database (TSC2): TSC2_00166; dbSNP: rs45509697
NCBI 1000 Genomes Browser:
rs45509697
Molecular consequence:
  • NM_000548.5:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001077183.3:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001114382.3:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318827.2:c.1146+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318829.2:c.1110+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318831.2:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001318832.2:c.1290+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363528.2:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370404.1:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001370405.1:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406663.1:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406664.1:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406665.1:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406667.1:c.1347+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406668.1:c.1347+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406670.1:c.1146+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406671.1:c.1245+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406673.1:c.1245+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406675.1:c.1110+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406676.1:c.1110+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406677.1:c.1200+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406678.1:c.1146+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406679.1:c.1110+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406680.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406681.1:c.795+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406682.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406683.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406684.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406685.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406686.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406687.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406688.1:c.657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406689.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406690.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406691.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406692.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406693.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406694.1:c.-56+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406695.1:c.-56+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406696.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406697.1:c.-88+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406698.1:c.-264+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_021055.3:c.1257+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000854626Baylor Genetics
no assertion criteria provided
Likely pathogenic
(Nov 18, 2018) 		germlineclinical testing

SCV002239062Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 6, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Molecular cloning of the alcohol/hydroxysteroid form (hSTa) of sulfotransferase from human liver.

Kong AN, Yang L, Ma M, Tao D, Bjornsson TD.

Biochem Biophys Res Commun. 1992 Aug 31;187(1):448-54.

PubMed [citation]
PMID:
1520333

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (5)

Details of each submission

From Baylor Genetics, SCV000854626.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002239062.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

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: 49683). This variant is also known as 1275+2T>C (Intron 11). Disruption of this splice site has been observed in individuals with tuberous sclerosis complex (PMID: 1520333, 10205261). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 12 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