NM_000551.4(VHL):c.154G>T (p.Glu52Ter) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000685691.8

Allele description [Variation Report for NM_000551.4(VHL):c.154G>T (p.Glu52Ter)]

NM_000551.4(VHL):c.154G>T (p.Glu52Ter)

Gene:

VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.154G>T (p.Glu52Ter)

Other names:

p.E52*:GAG>TAG

HGVS:

NC_000003.12:g.10142001G>T
NG_008212.3:g.5367G>T
NM_000551.4:c.154G>TMANE SELECT
NM_001354723.2:c.154G>T
NM_198156.3:c.154G>T
NP_000542.1:p.Glu52Ter
NP_000542.1:p.Glu52Ter
NP_001341652.1:p.Glu52Ter
NP_937799.1:p.Glu52Ter
LRG_322t1:c.154G>T
LRG_322:g.5367G>T
LRG_322p1:p.Glu52Ter
NC_000003.11:g.10183685G>T
NM_000551.3:c.154G>T
p.Glu52X

Protein change:

E52*

Links:

dbSNP: rs373068386

NCBI 1000 Genomes Browser:

rs373068386

Molecular consequence:

NM_000551.4:c.154G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354723.2:c.154G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198156.3:c.154G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Chuvash polycythemia
Synonyms:: POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
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

Recent activity

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PREDICTED: Momordica charantia uncharacterized LOC111013283 (LOC111013283), part...
PREDICTED: Momordica charantia uncharacterized LOC111013283 (LOC111013283), partial mRNA
gi|1229780339|ref|XM_022287712.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000813182	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26681312, 27651169, 28454591, 9671762, 9751722, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000813182

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

Gene panel sequencing improves the diagnostic work-up of patients with idiopathic erythrocytosis and identifies new mutations.

Camps C, Petousi N, Bento C, Cario H, Copley RR, McMullin MF, van Wijk R, Ratcliffe PJ, Robbins PA, Taylor JC; WGS500 Consortium..

Haematologica. 2016 Nov;101(11):1306-1318. Epub 2016 Sep 20.

PubMed [citation]

PMID:: 27651169
PMCID:: PMC5394871

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000813182.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Glu52*) in the VHL gene. It is unclear whether it will result in an absent or disrupted protein product because an in-frame methionine located at codon 54 has the potential to rescue this variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with VHL-related conditions (PMID: 26681312, 27651169, 28454591). ClinVar contains an entry for this variant (Variation ID: 182982). Several studies have shown that the VHL protein created from a downstream methionine located at codon 54 is biologically active, and exhibits properties similar to the full-length, wild-type protein (PMID: 9671762, 9751722). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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