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.124_126delCCCinsT (p.Pro42Serfs)

CA10580072

230956 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 88a545eb-341c-416c-944c-9454a71b04e5

HGVS expressions

NM_004360.4:c.124_126delCCCinsT
NM_004360.4(CDH1):c.124_126delCCCinsT (p.Pro42Serfs)
NC_000016.10:g.68738372_68738374delinsT
CM000678.2:g.68738372_68738374delinsT
NC_000016.9:g.68772275_68772277delinsT
CM000678.1:g.68772275_68772277delinsT
NC_000016.8:g.67329776_67329778delinsT
NG_008021.1:g.6081_6083delinsT
ENST00000261769.10:c.124_126delinsT
ENST00000261769.9:c.124_126delinsT
ENST00000422392.6:c.124_126delinsT
ENST00000566510.5:c.124_126delinsT
ENST00000566612.5:c.124_126delinsT
ENST00000611625.4:c.124_126delinsT
ENST00000612417.4:c.124_126delinsT
ENST00000621016.4:c.124_126delinsT
NM_004360.3:c.124_126delinsT
NM_001317184.1:c.124_126delinsT
NM_001317185.1:c.-1492_-1490delinsT
NM_001317186.1:c.-1696_-1694delinsT
NM_004360.4:c.124_126delinsT
NM_004360.5:c.124_126delinsT
NM_001317184.2:c.124_126delinsT
NM_001317185.2:c.-1492_-1490delinsT
NM_001317186.2:c.-1696_-1694delinsT
NM_004360.5(CDH1):c.124_126delinsT (p.Pro42fs)

Pathogenic

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

Evidence Links 1

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.124_126delCCCinsT (p.Pro42Serfs*16) 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 30745422). 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_Supporting, PM5_Supporting.
Met criteria codes
PVS1
This variant is predicted to result in a premature stop codon in exon 2 that leads to a truncated or absent protein.
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.
PS4_Supporting
This variant was identified in one family meeting IGCLC criteria for HDGC (PMID: 30745422).
This variant was identified in a family meeting IGCLC criteria for HDGC. PubMed:30745422
Not Met criteria codes
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
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.
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
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
Not applicable.
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.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable.
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
Not applicable.
Approved on: 2023-08-29
Published on: 2023-08-29
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