Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_004360.5(CDH1):c.1500C>T (p.Gly500=)

CA186535

183803 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2ea150e2-5fd5-4339-922c-efd411f12cf7
Approved on: 2023-08-28
Published on: 2023-09-27

HGVS expressions

NM_004360.5:c.1500C>T
NM_004360.5(CDH1):c.1500C>T (p.Gly500=)
NC_000016.10:g.68815694C>T
CM000678.2:g.68815694C>T
NC_000016.9:g.68849597C>T
CM000678.1:g.68849597C>T
NC_000016.8:g.67407098C>T
NG_008021.1:g.83403C>T
ENST00000261769.10:c.1500C>T
ENST00000261769.9:c.1500C>T
ENST00000422392.6:c.1317C>T
ENST00000562836.5:n.1571C>T
ENST00000566510.5:c.*166C>T
ENST00000566612.5:c.1500C>T
ENST00000611625.4:c.1563C>T
ENST00000612417.4:c.1500C>T
ENST00000621016.4:c.1500C>T
NM_004360.3:c.1500C>T
NM_001317184.1:c.1317C>T
NM_001317185.1:c.-49C>T
NM_001317186.1:c.-320C>T
NM_004360.4:c.1500C>T
NM_001317184.2:c.1317C>T
NM_001317185.2:c.-49C>T
NM_001317186.2:c.-320C>T
More

Likely Benign

Met criteria codes 3
BS2 BP7 BP4
Not Met criteria codes 12
PS4 PS1 PP4 PP2 PM3 PM1 PM2 PVS1 BA1 BS1 BP3 BP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The NM_004360.5:c.1500C>T (p.Gly500=) variant results in a synonymous amino acid variant within exon 10. This variant is present at an allele frequency of 0.00002828 (8/282862) in gnomAD v2.1.1, with a maximum frequency of 0.0003508 (7/19954) in the East Asian subpopulation. The variant has been observed in more than 10 (97) individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2). This variant occurs at a nucleotide that is not predicted to alter splicing or protein function by multiple in silico predictors (BP7, BP4). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4, BP7.
Met criteria codes
BS2
This variant has been observed in ~97 heterozygous individuals with no diffuse gastric cancer, signet ring cell carcinoma or lobular breast cancer and/or whose family histories do not suggest HDGC (BS2; GeneDX, Ambry, Invitae).
BP7
The NM_004360.5:c.1500C>T variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP4, BP7).
BP4
The results from 3 in silico predictors, SpliceAI, CADD and Netgene2, suggest that the variant does not impact CDH1 function (BP4).
Not Met criteria codes
PS4
No families meet HDGC criteria
PS1
Not applicable for CDH1
PP4
Not applicable for CDH1
PP2
Not applicable for CDH1
PM3
Not applicable for CDH1
PM1
Not applicable for CDH1
PM2
Minor allele frequencies (MAFs): East Asian sub-population (7/19954; 0.00035)
PVS1
The NM_004360.5:c.1500C>T variant is a synonymous (silent) variant.
BA1
Minor allele frequencies (MAFs): East Asian sub-population (7/19954; 0.00035)
BS1
Minor allele frequencies (MAFs): East Asian sub-population (7/19954; 0.00035)
BP3
Not applicable for CDH1
BP1
Not applicable for CDH1
Curation History
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