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NM_201253.3(CRB1):c.652+3_652+6del AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 4, 2020
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:
RCV001377781.6

Allele description [Variation Report for NM_201253.3(CRB1):c.652+3_652+6del]

NM_201253.3(CRB1):c.652+3_652+6del

Gene:
CRB1:crumbs cell polarity complex component 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1q31.3
Genomic location:
Preferred name:
NM_201253.3(CRB1):c.652+3_652+6del
HGVS:
  • NC_000001.11:g.197329006_197329009del
  • NG_008483.2:g.132545_132548del
  • NM_001193640.2:c.652+3_652+6del
  • NM_001257965.2:c.445+3_445+6del
  • NM_001257966.2:c.652+3_652+6del
  • NM_201253.3:c.652+3_652+6delMANE SELECT
  • NC_000001.10:g.197298134_197298137del
  • NC_000001.10:g.197298136_197298139del
  • NM_001257965.2:c.445+3_445+6delAAGT
Links:
dbSNP: rs1658700284
NCBI 1000 Genomes Browser:
rs1658700284
Molecular consequence:
  • NM_001193640.2:c.652+3_652+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001257965.2:c.445+3_445+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001257966.2:c.652+3_652+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_201253.3:c.652+3_652+6del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Retinitis pigmentosa 12 (RP12)
Synonyms:
RP 12; RP WITH OR WITHOUT PPRPE; RP WITH OR WITHOUT PRESERVED PARAARTERIOLE RETINAL PIGMENT EPITHELIUM; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010818; MedGen: C1838647; Orphanet: 791; OMIM: 600105
Name:
Leber congenital amaurosis 8 (LCA8)
Identifiers:
MONDO: MONDO:0013453; MedGen: C3151202; Orphanet: 65; OMIM: 613835

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001575204Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Mar 4, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001575204.4

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

Description

This sequence change falls in intron 2 of the CRB1 gene. It does not directly change the encoded amino acid sequence of the CRB1 protein, but it affects nucleotides within the consensus splice site of the intron. 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. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with early onset retinal dystrophy (PMID: 25323024). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Jun 23, 2024