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NM_004937.3(CTNS):c.61+2T>C AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 2, 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:
RCV002675467.9

Allele description [Variation Report for NM_004937.3(CTNS):c.61+2T>C]

NM_004937.3(CTNS):c.61+2T>C

Gene:
CTNS:cystinosin, lysosomal cystine transporter [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.2
Genomic location:
Preferred name:
NM_004937.3(CTNS):c.61+2T>C
HGVS:
  • NC_000017.11:g.3640269T>C
  • NG_012489.2:g.8802T>C
  • NG_052852.1:g.1054A>G
  • NM_001031681.3:c.61+2T>C
  • NM_001374492.1:c.61+2T>C
  • NM_001374493.1:c.-296+2T>C
  • NM_001374494.1:c.-381+2953T>C
  • NM_001374495.1:c.-217+2T>C
  • NM_001374496.1:c.-296+2953T>C
  • NM_004937.3:c.61+2T>CMANE SELECT
  • NC_000017.10:g.3543563T>C
Links:
dbSNP: rs767289120
NCBI 1000 Genomes Browser:
rs767289120
Molecular consequence:
  • NM_001374494.1:c.-381+2953T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001374496.1:c.-296+2953T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001031681.3:c.61+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374492.1:c.61+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374493.1:c.-296+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374495.1:c.-217+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004937.3:c.61+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Ocular cystinosis
Synonyms:
Cystinosis, ocular nonnephropathic; Cystinosis, adult, nonnephropathic; Cystinosis, benign, nonnephropathic
Identifiers:
MONDO: MONDO:0009064; MedGen: C2931013; Orphanet: 213; OMIM: 219750
Name:
Juvenile nephropathic cystinosis
Synonyms:
CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE
Identifiers:
MONDO: MONDO:0009066; MedGen: C0268626; Orphanet: 213; Orphanet: 411634; OMIM: 219900
Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002289563Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 2, 2021) 		germlineclinical testing

PubMed (4)
[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

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

A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.

Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, van't Hoff W, Antignac C.

Nat Genet. 1998 Apr;18(4):319-24.

PubMed [citation]
PMID:
9537412
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002289563.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CTNS-related conditions. This variant is present in population databases (rs767289120, ExAC 0.02%). This sequence change affects a donor splice site in intron 3 of the CTNS 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 CTNS are known to be pathogenic (PMID: 9537412, 27102039).

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

Last Updated: Sep 1, 2024