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_004360.3(CDH1):c.1711+1G>C

CA10603548

279747 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 25dd0b43-ea24-4a9a-9397-1d65b3e0cdba

HGVS expressions

NM_004360.3:c.1711+1G>C
NM_004360.3(CDH1):c.1711+1G>C
NC_000016.10:g.68819426G>C
CM000678.2:g.68819426G>C
NC_000016.9:g.68853329G>C
CM000678.1:g.68853329G>C
NC_000016.8:g.67410830G>C
NG_008021.1:g.87135G>C
ENST00000261769.10:c.1711+1G>C
ENST00000261769.9:c.1711+1G>C
ENST00000422392.6:c.1528+1G>C
ENST00000562836.5:n.1782+1G>C
ENST00000566510.5:c.*377+1G>C
ENST00000566612.5:c.1566-2575G>C
ENST00000611625.4:c.1774+1G>C
ENST00000612417.4:c.1711+1G>C
ENST00000621016.4:c.1711+1G>C
NM_001317184.1:c.1528+1G>C
NM_001317185.1:c.163+1G>C
NM_001317186.1:c.-254-2575G>C
NM_004360.4:c.1711+1G>C
NM_004360.5:c.1711+1G>C
NM_001317184.2:c.1528+1G>C
NM_001317185.2:c.163+1G>C
NM_001317186.2:c.-254-2575G>C
NM_004360.5(CDH1):c.1711+1G>C

Pathogenic

Met criteria codes 5
PVS1_Strong PS3 PS4_Moderate PM5_Supporting PM2_Supporting
Not Met criteria codes 21
PS2 PS1 BP5 BP7 BP2 BP3 BP4 BP1 PP4 PP1 PP3 PP2 BA1 PM6 PM3 PM1 PM4 BS2 BS4 BS3 BS1

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.1711+1G>C is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong, PM5_Supporting). RNA studies have demonstrated that this alteration results in abnormal out of frame splicing (PS3). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in three families meeting HDGC clinical criteria (PS4_Moderate; SCV000329230.6). 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_Strong, PM2_Supporting, PS3, PS4_Moderate, PM5_Supporting.
Met criteria codes
PVS1_Strong
Canonical donor splice site variant in intron 11, predicted to result in a truncated or absent protein
PS3
RNA studies have demonstrated that this alteration results in abnormal out of frame splicing (r.1566_1711del146 p.Y523Ffs*16; Laboratory internal data)
PS4_Moderate
Three families meet HDGC clinical criteria (SCV000329230.6; PMID: 12800196; PMID: 30306390; Laboratory internal data).
Identified as a somatic variant in an infiltrating lobular carcinoma. PubMed:12800196
PM5_Supporting
Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
PM2_Supporting
Absent in gnomAD
Not Met criteria codes
PS2
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
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
BP2
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
One meiosis across a single family (SCV000329230.6).
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
BA1
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
PM3
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
PM4
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: 2023-10-23
Published on: 2023-11-10
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