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NM_152564.5(VPS13B):c.6657+2T>C AND Cohen syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 28, 2019
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:
RCV001230895.8

Allele description [Variation Report for NM_152564.5(VPS13B):c.6657+2T>C]

NM_152564.5(VPS13B):c.6657+2T>C

Gene:
VPS13B:vacuolar protein sorting 13 homolog B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q22.2
Genomic location:
Preferred name:
NM_152564.5(VPS13B):c.6657+2T>C
HGVS:
  • NC_000008.11:g.99717375T>C
  • NG_007098.2:g.709110T>C
  • NM_017890.5:c.6732+2T>C
  • NM_152564.5:c.6657+2T>CMANE SELECT
  • LRG_351t1:c.6732+2T>C
  • LRG_351:g.709110T>C
  • NC_000008.10:g.100729603T>C
  • NM_017890.4:c.6732+2T>C
Links:
dbSNP: rs1832966881
NCBI 1000 Genomes Browser:
rs1832966881
Molecular consequence:
  • NM_017890.5:c.6732+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_152564.5:c.6657+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cohen syndrome (COH1)
Synonyms:
Pepper syndrome; Cutis verticis gyrata, retinitis pigmentosa, and sensorineural deafness
Identifiers:
MONDO: MONDO:0008999; MedGen: C0265223; Orphanet: 193; OMIM: 216550

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001403395Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 28, 2019) 		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

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

High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome.

Parri V, Katzaki E, Uliana V, Scionti F, Tita R, Artuso R, Longo I, Boschloo R, Vijzelaar R, Selicorni A, Brancati F, Dallapiccola B, Zelante L, Hamel CP, Sarda P, Lalani SR, Grasso R, Buoni S, Hayek J, Servais L, de Vries BB, Georgoudi N, et al.

Eur J Hum Genet. 2010 Oct;18(10):1133-40. doi: 10.1038/ejhg.2010.59. Epub 2010 May 12.

PubMed [citation]
PMID:
20461111
PMCID:
PMC2987453
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001403395.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). 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. Disruption of this splice site has been observed in individuals affected with Cohen syndrome (PMID: 15141358, 16648375, 25472526). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 37 of the VPS13B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

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

Last Updated: Sep 29, 2024