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.1566-1G>C

CA283310260

481704 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: aa9d80fe-4740-4b6b-99b4-743557f88750
Approved on: 2023-08-21
Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.1566-1G>C
NM_004360.5(CDH1):c.1566-1G>C
NC_000016.10:g.68819279G>C
CM000678.2:g.68819279G>C
NC_000016.9:g.68853182G>C
CM000678.1:g.68853182G>C
NC_000016.8:g.67410683G>C
NG_008021.1:g.86988G>C
ENST00000261769.10:c.1566-1G>C
ENST00000261769.9:c.1566-1G>C
ENST00000422392.6:c.1383-1G>C
ENST00000562836.5:n.1637-1G>C
ENST00000566510.5:c.*232-1G>C
ENST00000566612.5:c.1566-2722G>C
ENST00000611625.4:c.1629-1G>C
ENST00000612417.4:c.1566-1G>C
ENST00000621016.4:c.1566-1G>C
NM_004360.3:c.1566-1G>C
NM_001317184.1:c.1383-1G>C
NM_001317185.1:c.18-1G>C
NM_001317186.1:c.-254-2722G>C
NM_004360.4:c.1566-1G>C
NM_001317184.2:c.1383-1G>C
NM_001317185.2:c.18-1G>C
NM_001317186.2:c.-254-2722G>C
More

Uncertain Significance

Met criteria codes 3
PS4_Moderate PVS1_Moderate PM2_Supporting
Not Met criteria codes 23
PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4 PM5 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS1

Evidence Links 0

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.1566-1G>C variant is a canonical splice variant predicted to result in the use of a cryptic splice site which preserves the reading frame (PVS1_moderate). This variant is absent in the gnomAD v2.1.1 cohort. In the gnomAD v3 it has a frequency of 0.000006978 (1 of 143,302) with a maximum non-founder allele frequency of 0.00001549 (1 of 64,570) in the European non-Finnish subpopulation (PM2_supporting; http://gnomad.broadinstitute.org). The variant has been reported in two families meeting clinical criteria for HDGC (PS4_moderate, SCV000666335.2, internal laboratory contributor). In summary, the clinical significance of this variant is classified as of uncertain significance based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_moderate, PS4_moderate, PM2_supporting.
Met criteria codes
PS4_Moderate
Variant identified in two families meeting HDGC criteria
PVS1_Moderate
predicted in SpliceAI to result in the use of a cryptic splice site which preserves the reading frame
PM2_Supporting
variant is absent in gnomAD v2.1.1. Present in 1 of 64,570 alleles in the NFE subpopulation in gnomAD v3 (overall: 1 out of 143,302)
Not Met criteria codes
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
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
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
variant is absent in gnomAD v2.1.1. Present in 1 of 64,570 alleles in the NFE subpopulation in gnomAD v3 (overall: 1 out of 143,302)
BS2
Variant seen in >3 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC. BS2 cannot be applied to variants in which more than 30% of reported individuals meet HDGC criteria.
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
variant is absent in gnomAD v2.1.1. Present in 1 of 64,570 alleles in the NFE subpopulation in gnomAD v3 (overall: 1 out of 143,302)
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
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
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
Curation History
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