NM_004360.5(CDH1):c.1711+6G>A AND Hereditary diffuse gastric adenocarcinoma

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 15, 2024
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:: RCV000806794.10

Allele description [Variation Report for NM_004360.5(CDH1):c.1711+6G>A]

NM_004360.5(CDH1):c.1711+6G>A

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.1711+6G>A

HGVS:

NC_000016.10:g.68819431G>A
NG_008021.1:g.87140G>A
NM_001317184.2:c.1528+6G>A
NM_001317185.2:c.163+6G>A
NM_001317186.2:c.-254-2570G>A
NM_004360.4:c.1711+6G>A
NM_004360.5:c.1711+6G>AMANE SELECT
LRG_301t1:c.1711+6G>A
LRG_301:g.87140G>A
NC_000016.9:g.68853334G>A
NM_004360.3:c.1711+6G>A

Links:

dbSNP: rs1555516597

NCBI 1000 Genomes Browser:

rs1555516597

Molecular consequence:

NM_001317184.2:c.1528+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317185.2:c.163+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001317186.2:c.-254-2570G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_004360.5:c.1711+6G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Hereditary diffuse gastric adenocarcinoma (HDGC)
Synonyms:: DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME
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
SCV000946813	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 15, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532
SCV003926832	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

SCV000946813

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 15, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003926832

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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000946813.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change falls in intron 11 of the CDH1 gene. It does not directly change the encoded amino acid sequence of the CDH1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 651431). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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

From European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto - ERN GENTURIS, SCV003926832.1

#	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: Feb 25, 2025

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