NM_004360.5(CDH1):c.249T>C (p.Ile83=) AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 5, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001488332.17

Allele description [Variation Report for NM_004360.5(CDH1):c.249T>C (p.Ile83=)]

NM_004360.5(CDH1):c.249T>C (p.Ile83=)

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.249T>C (p.Ile83=)

HGVS:

NC_000016.10:g.68801755T>C
NG_008021.1:g.69464T>C
NM_001317184.2:c.249T>C
NM_001317185.2:c.-1367T>C
NM_001317186.2:c.-1571T>C
NM_004360.5:c.249T>CMANE SELECT
NP_001304113.1:p.Ile83=
NP_004351.1:p.Ile83=
LRG_301t1:c.249T>C
LRG_301:g.69464T>C
NC_000016.9:g.68835658T>C
NM_004360.3:c.249T>C
NM_004360.4:c.249T>C

Links:

dbSNP: rs878854687

NCBI 1000 Genomes Browser:

rs878854687

Molecular consequence:

NM_001317185.2:c.-1367T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317186.2:c.-1571T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001317184.2:c.249T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_004360.5:c.249T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Name:: Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:: Hereditary diffuse gastric cancer
Identifiers:: MONDO: MONDO:0007648; MedGen: C1708349; Orphanet: 26106; OMIM: 137215

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001692842	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Feb 5, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003927009	European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS	criteria provided, single submitter (Lee et al. (Hum Mutat. 2018))	Uncertain significance (Aug 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30311375, 36436516

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001692842

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Feb 5, 2023)

germline

clinical testing

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

SCV003927009

European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS

criteria provided, single submitter

(Lee et al. (Hum Mutat. 2018))

Uncertain significance
(Aug 1, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants.

Lee K, Krempely K, Roberts ME, Anderson MJ, Carneiro F, Chao E, Dixon K, Figueiredo J, Ghosh R, Huntsman D, Kaurah P, Kesserwan C, Landrith T, Li S, Mensenkamp AR, Oliveira C, Pardo C, Pesaran T, Richardson M, Slavin TP, Spurdle AB, Trapp M, et al.

Hum Mutat. 2018 Nov;39(11):1553-1568. doi: 10.1002/humu.23650.

PubMed [citation]

PMID:: 30311375
PMCID:: PMC6188664

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001692842.4

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

#	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

From European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS, SCV003927009.1

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

Description

"1 family not fulfilling 2020 HDGC criteria-Familial history of breast cancer"

PubMed [ID: 36436516]

Description

PM2 (PMID: 30311375)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	1	not provided

Last Updated: Nov 3, 2024

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