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]
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Variant: NM_004360.5(CDH1):c.300C>G (p.Val100=)

CA188969

184437 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9ad7cade-cab1-4844-8cb2-d1918d9a9717
Approved on: 2023-08-02
Published on: 2023-08-02

HGVS expressions

NM_004360.5:c.300C>G
NM_004360.5(CDH1):c.300C>G (p.Val100=)
NC_000016.10:g.68801806C>G
CM000678.2:g.68801806C>G
NC_000016.9:g.68835709C>G
CM000678.1:g.68835709C>G
NC_000016.8:g.67393210C>G
NG_008021.1:g.69515C>G
ENST00000261769.10:c.300C>G
ENST00000261769.9:c.300C>G
ENST00000422392.6:c.300C>G
ENST00000561751.1:n.67C>G
ENST00000562836.5:n.371C>G
ENST00000564676.5:n.582C>G
ENST00000564745.1:n.295C>G
ENST00000566510.5:c.300C>G
ENST00000566612.5:c.300C>G
ENST00000611625.4:c.300C>G
ENST00000612417.4:c.300C>G
ENST00000621016.4:c.300C>G
NM_004360.3:c.300C>G
NM_001317184.1:c.300C>G
NM_001317185.1:c.-1316C>G
NM_001317186.1:c.-1520C>G
NM_004360.4:c.300C>G
NM_001317184.2:c.300C>G
NM_001317185.2:c.-1316C>G
NM_001317186.2:c.-1520C>G
More

Likely Benign

Met criteria codes 3
BS2 BP4 PM2_Supporting
Not Met criteria codes 23
PVS1 BA1 BS4 BS3 BS1 BP3 BP2 BP1 BP5 BP7 PS2 PS3 PS4 PS1 PP4 PP1 PP3 PP2 PM6 PM1 PM4 PM3 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.300C>G variant (NM_004360.5) is a synonymous (silent) variant (p.Val100=) that is not predicted by SpliceAI, varSEAK, to impact splicing (BP4). Although this variant is absent in gnomAD v2.1.1 and v3.1 (PM2_Supporting), it has been observed in more than 10 heterozygous individuals with no DCG, SRC tumours, or LBC and whose families do not suggest HDGC (BS2; Ambry Genetics, Invitae, University of Washington). In summary, although there are both pathogenic and benign types of evidence for this variant, the CDH1 VCEP classified the variant as likely benign for DGLBCS based on BS2 alone. (CDH1 VCEP specifications version 3.1; 05/06/2022)
Met criteria codes
BS2
This variant has been observed in more than 10 heterozygous individuals with no DCG, SRC tumours, or LBC and whose families do not suggest HDGC (BS2; Ambry Genetics, Invitae, University of Washington).
BP4
The results from >3 in silico predictors, [SpliceAI - acceptor gain 0.01 -14 bp, donor gain 0.00 varSEAK - no splicing impact MaxEntScan - no splicing impact] display no impact to CDH1 function (BP4).
PM2_Supporting
This variant is absent in gnomAD v2.1.1 and v3.1 (PM2_Supporting).
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
G is not reference in any primates, and reference in only 1 mammal (shrew)
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No families that meet HDGC clinical criteria. 3 families with insufficient evidence to determine if HDGC clinical criteria would be met (Ambry Genetics, Invitae).
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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