Evidence Repository - Clinical Genome Resources

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

Likely Benign

PM2_Supporting BS2 BP4

BS4 BS3 BS1 PVS1 BP5 BP7 BP3 BP2 BP1 PS2 PS3 PS4 PS1 BA1 PP4 PP1 PP3 PP2 PM6 PM1 PM4 PM3 PM5

Evidence Links 0

Expert Panel

CDH1 VCEP

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)

PM2_Supporting

This variant is absent in gnomAD v2.1.1 and v3.1 (PM2_Supporting).

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).

BS4