NM_000551.4(VHL):c.104C>A (p.Ala35Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 15, 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:: RCV001017126.3

Allele description [Variation Report for NM_000551.4(VHL):c.104C>A (p.Ala35Asp)]

NM_000551.4(VHL):c.104C>A (p.Ala35Asp)

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.104C>A (p.Ala35Asp)

HGVS:

NC_000003.12:g.10141951C>A
NG_008212.3:g.5317C>A
NM_000551.4:c.104C>AMANE SELECT
NM_001354723.2:c.104C>A
NM_198156.3:c.104C>A
NP_000542.1:p.Ala35Asp
NP_000542.1:p.Ala35Asp
NP_001341652.1:p.Ala35Asp
NP_937799.1:p.Ala35Asp
LRG_322t1:c.104C>A
LRG_322:g.5317C>A
LRG_322p1:p.Ala35Asp
NC_000003.11:g.10183635C>A
NM_000551.3:c.104C>A

Protein change:

A35D

Links:

dbSNP: rs587780536

NCBI 1000 Genomes Browser:

rs587780536

Molecular consequence:

NM_000551.4:c.104C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.104C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.104C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV001178158	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Sep 10, 2021)	germline	clinical testing	Citation Link,
SCV002534134	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Oct 15, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001178158

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Sep 10, 2021)

germline

clinical testing

Citation Link,

SCV002534134

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Oct 15, 2021)

germline

curation

Citation Link

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	1	not provided	clinical testing, curation

Details of each submission

From Ambry Genetics, SCV001178158.3

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

Description

The p.A35D variant (also known as c.104C>A), located in coding exon 1 of the VHL gene, results from a C to A substitution at nucleotide position 104. The alanine at codon 35 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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	1	not provided	not provided		1	not provided	not provided	not provided

From Sema4, Sema4, SCV002534134.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	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: Mar 5, 2024

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