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]
Link to SEPIO compliant JSON-LD document

Variant: NM_004360.4(CDH1):c.59G>A (p.Trp20Ter)

CA280996

12239 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7421ee61-7174-481d-b6bd-1800d58e9755

HGVS expressions

NM_004360.4:c.59G>A
NM_004360.4(CDH1):c.59G>A (p.Trp20Ter)
NC_000016.10:g.68738307G>A
CM000678.2:g.68738307G>A
NC_000016.9:g.68772210G>A
CM000678.1:g.68772210G>A
NC_000016.8:g.67329711G>A
NG_008021.1:g.6016G>A
ENST00000261769.10:c.59G>A
ENST00000261769.9:c.59G>A
ENST00000422392.6:c.59G>A
ENST00000566510.5:c.59G>A
ENST00000566612.5:c.59G>A
ENST00000611625.4:c.59G>A
ENST00000612417.4:c.59G>A
ENST00000621016.4:c.59G>A
NM_004360.3:c.59G>A
NM_001317184.1:c.59G>A
NM_001317185.1:c.-1557G>A
NM_001317186.1:c.-1761G>A
NM_004360.5:c.59G>A
NM_001317184.2:c.59G>A
NM_001317185.2:c.-1557G>A
NM_001317186.2:c.-1761G>A
NM_004360.5(CDH1):c.59G>A (p.Trp20Ter)

Pathogenic

Met criteria codes 4
PS4_Moderate PVS1 PM5_Supporting PM2_Supporting
Not Met criteria codes 22
BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM6 BA1 BS2 BS4 BS3 BS1

Evidence Links 3

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.59G>A (p.Trp20*) variant is predicted to result in a premature stop codon in exon 2 that leads to a truncated or absent protein (PVS1, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least two families meeting HDGC clinical criteria (PS4_Moderate; PMID: 10072428, 26182300). In summary, 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_Moderate, PM5_Supporting.
Met criteria codes
PS4_Moderate
This variant was identified in two families meeting IGCLC criteria for HDGC (PMID: 10072428, 26182300).
This variant was identified in one family meeting IGCLC criteria for HDGC. PubMed:26182300
This variant was reported as a somatic event in an individual with lobular breast cancer. This variant is also reported as a somatic mutation in two breast tumours (COSMIC ID: COSM19502). PubMed:10094558
This variant was identified in an individual with a personal and family history of diffuse gastric cancer. PubMed:10072428
PVS1
This variant is predicted to result in a premature stop codon in exon 2.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
Allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.
Not Met criteria codes
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Not applicable.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable.
BP4
Not applicable.
BP1
Not applicable.
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Not applicable.
PP2
Not applicable.
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
PM4
Not applicable.
PM6
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
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
Approved on: 2023-08-29
Published on: 2023-08-29
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