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NM_000551.4(VHL):c.-61_-51dup AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 7, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000152655.9

Allele description [Variation Report for NM_000551.4(VHL):c.-61_-51dup]

NM_000551.4(VHL):c.-61_-51dup

Gene:
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_000551.4(VHL):c.-61_-51dup
HGVS:
  • NC_000003.11:g.10183466_10183467insTCCGCCCCGCG
  • NC_000003.12:g.10141787_10141797dup
  • NG_008212.3:g.5153_5163dup
  • NM_000551.4:c.-61_-51dupMANE SELECT
  • NM_001354723.2:c.-61_-51dup
  • NM_198156.3:c.-61_-51dup
  • LRG_322t1:c.-61_-51dup
  • LRG_322:g.5153_5163dup
  • NC_000003.11:g.10183466_10183467insTCCGCCCCGCG
  • NC_000003.11:g.10183471_10183481dup
  • NC_000003.11:g.10183481_10183482insCCCCGCGTCCG
  • NM_000551.2:c.-61_-51dup
  • NM_000551.3:c.-61_-51dup
Links:
dbSNP: rs727503743
NCBI 1000 Genomes Browser:
rs727503743
Molecular consequence:
  • NM_000551.4:c.-61_-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354723.2:c.-61_-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_198156.3:c.-61_-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000202007Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Dec 10, 2014) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002068830Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 7, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided21not providednot providednot providedclinical testing

Citations

PubMed

Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter.

Zatyka M, Morrissey C, Kuzmin I, Lerman MI, Latif F, Richards FM, Maher ER.

J Med Genet. 2002 Jul;39(7):463-72.

PubMed [citation]
PMID:
12114475
PMCID:
PMC1735189

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000202007.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The c.-61_-51dup variant in VHL has previously been identified by our laboratory in 1 individual with VHL. Data from large population studies is insufficient to assess the frequency of this variant. This variant is located in the 5' untrans lated region (UTR) and variants in regulatory regions could have an effect on tr anscriptional or translational efficiency. Studies have shown that sequence alte rations in this region may alter VHL transcription (Zatyka 2002) and our laborat ory has identified a 5' UTR deletion variant in VHL overlapping with this region that segregated with disease in multiple affected individuals (LMM unpublished data). However, in the absence of additional information, further data is needed to fully assess the clinical significance of this variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

From Genetic Services Laboratory, University of Chicago, SCV002068830.1

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

Description

DNA sequence analysis of the VHL gene demonstrated an 11 base pair duplication in the 5' untranslated region, c.-61_-51dup. This change has been previously described in an individual with a single renal cyst and his apparently asymptomatic daughter, both of whom did not fulfill clinical diagnostic criteria of VHL-related disorder (PMID: 30006056). Western blotting and VHL transcript analysis showed milder reduction of VHL gene expression. This sequence change has been described in the gnomAD with a low population frequency of 0.0096% (dbSNP rs529928317). The functional significance of this sequence change is not clearly established at present and its contribution to this patient's disease phenotype cannot definitively be determined.

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

Last Updated: May 12, 2024