NM_000551.4(VHL):c.483_500dup (p.Cys162_Arg167dup) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001373035.1

Allele description [Variation Report for NM_000551.4(VHL):c.483_500dup (p.Cys162_Arg167dup)]

NM_000551.4(VHL):c.483_500dup (p.Cys162_Arg167dup)

Genes:
LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [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.483_500dup (p.Cys162_Arg167dup)
HGVS:
  • NC_000003.12:g.10149806_10149823dup
  • NG_008212.3:g.13172_13189dup
  • NG_046756.1:g.7568_7585dup
  • NM_000551.3:c.483_500dup
  • NM_000551.4:c.483_500dupMANE SELECT
  • NM_001354723.2:c.*37_*54dup
  • NM_198156.3:c.360_377dup
  • NP_000542.1:p.Cys162_Arg167dup
  • NP_000542.1:p.Cys162_Arg167dup
  • NP_937799.1:p.Cys121_Arg126dup
  • LRG_322t1:c.483_500dup
  • LRG_322:g.13172_13189dup
  • LRG_322p1:p.Cys162_Arg167dup
  • NC_000003.11:g.10191487_10191488insCGATGCCTCCAGGTTGTC
  • NC_000003.11:g.10191490_10191507dup
  • NM_000551.3:c.483_500dupATGCCTCCAGGTTGTCCG
Links:
dbSNP: rs1553620312
NCBI 1000 Genomes Browser:
rs1553620312
Molecular consequence:
  • NM_001354723.2:c.*37_*54dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.483_500dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_198156.3:c.360_377dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:
Erythrocytosis, familial, 2 (ECYT2)
Synonyms:
POLYCYTHEMIA, CHUVASH TYPE; POLYCYTHEMIA, VHL-DEPENDENT
Identifiers:
MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400
Name:
Von Hippel-Lindau syndrome (VHLS)
Synonyms:
VHL syndrome; Von Hippel-Lindau
Identifiers:
MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001569733Invitaecriteria provided, single submitter
Uncertain significance
(Oct 4, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001569733.1

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

Description

This variant, c.483_500dup, results in the insertion of 6 amino acid(s) to the VHL protein (p.Cys162_Arg167dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of von Hippel-Lindau syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 480846). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 25, 2021

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