NM_000551.4(VHL):c.429C>T (p.Asp143=) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 27, 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:: RCV000564320.5

Allele description [Variation Report for NM_000551.4(VHL):c.429C>T (p.Asp143=)]

NM_000551.4(VHL):c.429C>T (p.Asp143=)

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:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.429C>T (p.Asp143=)

HGVS:

NC_000003.12:g.10146602C>T
NG_008212.3:g.9968C>T
NG_046756.1:g.4364C>T
NM_000551.4:c.429C>TMANE SELECT
NM_001354723.2:c.*18-3185C>T
NM_198156.3:c.341-3185C>T
NP_000542.1:p.Asp143=
NP_000542.1:p.Asp143=
LRG_322t1:c.429C>T
LRG_322:g.9968C>T
LRG_322p1:p.Asp143=
NC_000003.11:g.10188286C>T
NM_000551.3:c.429C>T

Links:

dbSNP: rs773556807

NCBI 1000 Genomes Browser:

rs773556807

Molecular consequence:

NM_001354723.2:c.*18-3185C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3185C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.429C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000664611	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000664611

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 27, 2023)

germline

clinical testing

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

Citation Link

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

Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.

Lenglet M, Robriquet F, Schwarz K, Camps C, Couturier A, Hoogewijs D, Buffet A, Knight SJL, Gad S, Couvé S, Chesnel F, Pacault M, Lindenbaum P, Job S, Dumont S, Besnard T, Cornec M, Dreau H, Pentony M, Kvikstad E, Deveaux S, Burnichon N, et al.

Blood. 2018 Aug 2;132(5):469-483. doi: 10.1182/blood-2018-03-838235. Epub 2018 Jun 11.

PubMed [citation]

PMID:: 29891534

Details of each submission

From Ambry Genetics, SCV000664611.6

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

Description

The c.429C>T variant (also known as p.D143D), located in coding exon 2 of the VHL gene, results from a C to T substitution at nucleotide position 429. This nucleotide substitution does not change the aspartic acid at codon 143. This variant has been identified in the homozygous state and in trans with a VHL variant in individuals diagnosed with erythrocytosis (Lenglet M et al. Blood, 2018 Aug;132:469-483). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, RNA studies have detected abnormal splicing associated with this variant (Lenglet M et al. Blood, 2018 Aug;132:469-483, Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Oct 20, 2024

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