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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_004360.4(CDH1):c.1895_1896delAC (p.His632Argfs)

CA16615404

406628 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 65458bc2-ea32-41ce-87e1-c4fc4183acdc
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.4:c.1895_1896del
NM_004360.4(CDH1):c.1895_1896delAC (p.His632Argfs)
NC_000016.10:g.68822184_68822185del
CM000678.2:g.68822184_68822185del
NC_000016.9:g.68856087_68856088del
CM000678.1:g.68856087_68856088del
NC_000016.8:g.67413588_67413589del
NG_008021.1:g.89893_89894del
ENST00000261769.10:c.1895_1896del
ENST00000261769.9:c.1895_1896del
ENST00000422392.6:c.1712_1713del
ENST00000562836.5:n.1966_1967del
ENST00000566510.5:c.*561_*562del
ENST00000566612.5:c.*135_*136del
ENST00000611625.4:c.1958_1959del
ENST00000612417.4:c.1830+65_1830+66del
ENST00000621016.4:c.1865+30_1865+31del
NM_004360.3:c.1895_1896del
NM_001317184.1:c.1712_1713del
NM_001317185.1:c.347_348del
NM_001317186.1:c.-71_-70del
NM_004360.5:c.1895_1896del
NM_001317184.2:c.1712_1713del
NM_001317185.2:c.347_348del
NM_001317186.2:c.-71_-70del
More

Pathogenic

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

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.1895_1896delAC (p.His632ArgfsTer30) 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 two familes meeting HDGC clinical criteria (PS4_Moderate; PMID 26182300, https://doi.org/10.2147/GICTT.S16330). 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
At least 2 families meeting HDGC clinical criteria (PMID: 26182300, Shenoy et al. 2011 - https://doi.org/10.2147/GICTT.S16330: extensive FH of gastric cancer, and case diagnosed with LBC and in situ SRC carcinoma detected in path specimen of gastrectomy).
Variant identified in an unaffected index case meeting IGCLC 2010 clinical criteria for HDGC due to Family history of DGC PubMed:26182300
PVS1
A 2 bp deletion in exon 12/16, predicted to result in a truncated or absent protein
PM2_Supporting
Absent in gnomAD
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
Not Met criteria codes
BS1
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
BS2
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
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
BP3
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
PS1
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
PS3
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
PP1
Shenoy et al. 2011 - https://doi.org/10.2147/GICTT.S16330: two affected segregations, and apparent incomplete penetrance
PP2
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
PP4
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
PM4
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
Curation History
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