NM_004360.5(CDH1):c.286A>T (p.Ile96Phe) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 1, 2021
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:: RCV001375526.1

Allele description [Variation Report for NM_004360.5(CDH1):c.286A>T (p.Ile96Phe)]

NM_004360.5(CDH1):c.286A>T (p.Ile96Phe)

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.286A>T (p.Ile96Phe)

HGVS:

NC_000016.10:g.68801792A>T
NG_008021.1:g.69501A>T
NM_001317184.2:c.286A>T
NM_001317185.2:c.-1330A>T
NM_001317186.2:c.-1534A>T
NM_004360.5:c.286A>TMANE SELECT
NP_001304113.1:p.Ile96Phe
NP_004351.1:p.Ile96Phe
LRG_301t1:c.286A>T
LRG_301:g.69501A>T
NC_000016.9:g.68835695A>T
NM_004360.3:c.286A>T
NM_004360.4:c.286A>T
p.I96F

Protein change:

I96F

Links:

dbSNP: rs749306433

NCBI 1000 Genomes Browser:

rs749306433

Molecular consequence:

NM_001317185.2:c.-1330A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1534A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.286A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004360.5:c.286A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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Mus musculus cell division cycle 25B (Cdc25b), transcript variant 2, mRNA
Mus musculus cell division cycle 25B (Cdc25b), transcript variant 2, mRNA
gi|380748970|ref|NM_001111075.4|

Nucleotide
Homo sapiens bone morphogenetic protein receptor type 1B (BMPR1B), RefSeqGene on...
Homo sapiens bone morphogenetic protein receptor type 1B (BMPR1B), RefSeqGene on chromosome 4
gi|219521908|ref|NG_009245.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001572383	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 1, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28580595, 33471991 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001572383

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 1, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Mutation screening of 10 cancer susceptibility genes in unselected breast cancer patients.

Xie Y, Li G, Chen M, Guo X, Tang L, Luo X, Wang S, Yi W, Dai L, Wang J.

Clin Genet. 2018 Jan;93(1):41-51. doi: 10.1111/cge.13063. Epub 2017 Sep 25.

PubMed [citation]

PMID:: 28580595

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001572383.1

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

Description

Variant summary: CDH1 c.286A>T (p.Ile96Phe) results in a non-conservative amino acid change located in the prodomain (IPR014868) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251330 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.286A>T, has been reported in the literature in an individual affected with Breast Cancer (Xie_2018). However, a recent large-scale Breast Cancer study reported the variant in 4/60466 cases and 5/53461 controls, i.e. with a calculated odds ratio of 0.7, which suggests that this variant is not associated with a risk for Breast Cancer (Dorling_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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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