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.377del (p.Pro126fs)

CA16614939

406616 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ada0fe2a-2b8f-4adf-884f-b6724e44c863
Approved on: 2023-08-28
Published on: 2023-08-28

HGVS expressions

NM_004360.5:c.377del
NM_004360.5(CDH1):c.377del (p.Pro126fs)
NC_000016.10:g.68801883del
CM000678.2:g.68801883del
NC_000016.9:g.68835786del
CM000678.1:g.68835786del
NC_000016.8:g.67393287del
NG_008021.1:g.69592del
ENST00000261769.10:c.377del
ENST00000261769.9:c.377del
ENST00000422392.6:c.377del
ENST00000561751.1:n.144del
ENST00000562836.5:n.448del
ENST00000564676.5:n.659del
ENST00000564745.1:n.372del
ENST00000566510.5:c.377del
ENST00000566612.5:c.377del
ENST00000611625.4:c.377del
ENST00000612417.4:c.377del
ENST00000621016.4:c.377del
NM_004360.3:c.377del
NM_001317184.1:c.377del
NM_001317185.1:c.-1239del
NM_001317186.1:c.-1443del
NM_004360.4:c.377del
NM_001317184.2:c.377del
NM_001317185.2:c.-1239del
NM_001317186.2:c.-1443del
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Pathogenic

Met criteria codes 4
PM5_Supporting PM2_Supporting PS4_Supporting PVS1
Not Met criteria codes 22
PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM6 PM4 PM1 PM3 BA1 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2

Evidence Links 2

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 c.377delC p.(Pro126Argfs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 10433926). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.
Met criteria codes
PM5_Supporting
Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
PM2_Supporting
Absent in population databases.
PS4_Supporting
Proband with diffuse gastric cancer under 40 yo, and her mother with lobular breast (49 yo) and diffuse gastric cancer (58 yo) (PMID: 10433926).
Found in one patient with diffuse gastric cancer <40 yo. The same germline variant was also found in the patient's mother, who had metachronous development of lobular breast (49yo) and diffuse type gastric carcinomas (58yo). PubMed:10433926
Table 1 - review of the literature. PubMed:17545690
PVS1
Predicted NMD.
Not Met criteria codes
PS1
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
PS2
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
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
PM6
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
PM1
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
BS4
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
BP7
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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