NM_000551.4(VHL):c.280G>A (p.Glu94Lys) AND Von Hippel-Lindau syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 3, 2023
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:: RCV003997420.2

Allele description [Variation Report for NM_000551.4(VHL):c.280G>A (p.Glu94Lys)]

NM_000551.4(VHL):c.280G>A (p.Glu94Lys)

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.280G>A (p.Glu94Lys)

HGVS:

NC_000003.12:g.10142127G>A
NG_008212.3:g.5493G>A
NM_000551.4:c.280G>AMANE SELECT
NM_001354723.2:c.280G>A
NM_198156.3:c.280G>A
NP_000542.1:p.Glu94Lys
NP_000542.1:p.Glu94Lys
NP_001341652.1:p.Glu94Lys
NP_937799.1:p.Glu94Lys
LRG_322t1:c.280G>A
LRG_322:g.5493G>A
LRG_322p1:p.Glu94Lys
NC_000003.11:g.10183811G>A
NM_000551.3:c.280G>A
p.E94K

Protein change:

E94K

Links:

dbSNP: rs5030829

NCBI 1000 Genomes Browser:

rs5030829

Molecular consequence:

NM_000551.4:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.280G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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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Homo sapiens semaphorin 6B (SEMA6B), mRNA
Homo sapiens semaphorin 6B (SEMA6B), mRNA
gi|312836842|ref|NM_032108.3|

Nucleotide
Costal cartilage calcification
Costal cartilage calcification

MedGen
C1855608[conceptid] (1)
MedGen
Cystic lesions of the pinnae
Cystic lesions of the pinnae

MedGen
C4023720[conceptid] (1)
MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004820570	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Apr 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25952756, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004820570

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Apr 3, 2023)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian families.

Vikkath N, Valiyaveedan S, Nampoothiri S, Radhakrishnan N, Pillai GS, Nair V, Pooleri GK, Mathew G, Menon KN, Ariyannur PS, Pillai AB.

Fam Cancer. 2015 Dec;14(4):585-94. doi: 10.1007/s10689-015-9806-z.

PubMed [citation]

PMID:: 25952756

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004820570.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces glutamic acid with lysine at codon 94 of the VHL protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with von Hippel-Lindau syndrome (PMID: 25952756). This variant has been identified in 1/224192 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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