NM_004360.5(CDH1):c.182_183delinsGTG (p.Thr61fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 25, 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:: RCV003311331.2

Allele description [Variation Report for NM_004360.5(CDH1):c.182_183delinsGTG (p.Thr61fs)]

NM_004360.5(CDH1):c.182_183delinsGTG (p.Thr61fs)

Gene:

CDH1:cadherin 1 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_004360.5(CDH1):c.182_183delinsGTG (p.Thr61fs)

HGVS:

NC_000016.10:g.68801688_68801689delinsGTG
NG_008021.1:g.69397_69398delinsGTG
NM_001317184.2:c.182_183delinsGTG
NM_001317185.2:c.-1434_-1433delinsGTG
NM_001317186.2:c.-1638_-1637delinsGTG
NM_004360.5:c.182_183delinsGTGMANE SELECT
NP_001304113.1:p.Thr61fs
NP_004351.1:p.Thr61Serfs
NP_004351.1:p.Thr61fs
LRG_301t1:c.182_183delCCinsGTG
LRG_301:g.69397_69398delinsGTG
LRG_301p1:p.Thr61Serfs
NC_000016.9:g.68835591_68835592delinsGTG
NM_004360.3:c.182_183delCCinsGTG

Protein change:

T61fs

Molecular consequence:

NM_001317185.2:c.-1434_-1433delinsGTG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1638_-1637delinsGTG - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.182_183delinsGTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004360.5:c.182_183delinsGTG - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Hypothyroidism
Hypothyroidism
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there...<br/>

MeSH
Congenital Hypothyroidism
Congenital Hypothyroidism
A condition in infancy or early childhood due to an in-utero deficiency of THYROID HORMONES that can be caused by genetic or environmental factors, such as thyroid dysgenesis ...<br/>Year introduced: 2006 (1966)

MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004008256	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 25, 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

SCV004008256

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 25, 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

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 Ambry Genetics, SCV004008256.2

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

Description

The c.182_183delCCinsGTG pathogenic mutation, located in coding exon 3 of the CDH1 gene, results from the deletion of two nucleotides and insertion of 3 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.T61Sfs*33). This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med 2021 02;384:428-439). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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

ClinVar

Relating variation to medicine