NM_004360.5(CDH1):c.2573A>T (p.Asp858Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 12, 2022
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:: RCV002426020.2

Allele description [Variation Report for NM_004360.5(CDH1):c.2573A>T (p.Asp858Val)]

NM_004360.5(CDH1):c.2573A>T (p.Asp858Val)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.2573A>T (p.Asp858Val)

HGVS:

NC_000016.10:g.68833423A>T
NG_008021.1:g.101132A>T
NM_001317184.2:c.2390A>T
NM_001317185.2:c.1025A>T
NM_001317186.2:c.608A>T
NM_004360.5:c.2573A>TMANE SELECT
NP_001304113.1:p.Asp797Val
NP_001304114.1:p.Asp342Val
NP_001304115.1:p.Asp203Val
NP_004351.1:p.Asp858Val
NP_004351.1:p.Asp858Val
LRG_301t1:c.2573A>T
LRG_301:g.101132A>T
LRG_301p1:p.Asp858Val
NC_000016.9:g.68867326A>T
NM_004360.3:c.2573A>T

Protein change:

D203V

Molecular consequence:

NM_001317184.2:c.2390A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001317185.2:c.1025A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001317186.2:c.608A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.2573A>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002743073	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 12, 2022)	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

SCV002743073

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 12, 2022)

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

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

Pritchard AL, Johansson PA, Nathan V, Howlie M, Symmons J, Palmer JM, Hayward NK.

PLoS One. 2018;13(4):e0194098. doi: 10.1371/journal.pone.0194098.

PubMed [citation]

PMID:: 29641532
PMCID:: PMC5894988

Details of each submission

From Ambry Genetics, SCV002743073.2

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

Description

The p.D858V variant (also known as c.2573A>T), located in coding exon 16 of the CDH1 gene, results from an A to T substitution at nucleotide position 2573. The aspartic acid at codon 858 is replaced by valine, an amino acid with highly dissimilar properties. This alteration was identified in 2/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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