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_004360.5(CDH1):c.387+6T>C

CA8129842

387275 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 97db6d07-6a71-4289-b5a6-73e42e828486

HGVS expressions

NM_004360.5:c.387+6T>C
NM_004360.5(CDH1):c.387+6T>C
NC_000016.10:g.68801899T>C
CM000678.2:g.68801899T>C
NC_000016.9:g.68835802T>C
CM000678.1:g.68835802T>C
NC_000016.8:g.67393303T>C
NG_008021.1:g.69608T>C
ENST00000261769.10:c.387+6T>C
ENST00000261769.9:c.387+6T>C
ENST00000422392.6:c.387+6T>C
ENST00000561751.1:n.154+6T>C
ENST00000562836.5:n.458+6T>C
ENST00000564676.5:n.669+6T>C
ENST00000564745.1:n.382+6T>C
ENST00000566510.5:c.387+6T>C
ENST00000566612.5:c.387+6T>C
ENST00000611625.4:c.387+6T>C
ENST00000612417.4:c.387+6T>C
ENST00000621016.4:c.387+6T>C
NM_004360.3:c.387+6T>C
NM_001317184.1:c.387+6T>C
NM_001317185.1:c.-1229+6T>C
NM_001317186.1:c.-1433+6T>C
NM_004360.4:c.387+6T>C
NM_001317184.2:c.387+6T>C
NM_001317185.2:c.-1229+6T>C
NM_001317186.2:c.-1433+6T>C

Likely Benign

Met criteria codes 2
BS2 BP4
Not Met criteria codes 24
PVS1 BS4 BS3 BS1 BP2 BP3 BP1 BP5 BP7 PS4 PS2 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM5 PM6 PM2

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
c.387+6T>C is an intronic variant in the splice donor region of intron 3. This variant has an allele frequency of 0.0001 (5/34548 alleles) in the gnomAD v2.1 Latino/admixed American sub-population (http://gnomad.broadinstitute.org). This variant has been reported in at least 13 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000637825.4). This variant is predicted to have no impact on splicing by multiple in silico splice site predictors (BP4; SpliceAI, varSEAK, MaxEntScan). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4.
Met criteria codes
BS2
13 (>10) individuals w/o DCG, SRC tumours, or LBC & whose families do not suggest HDGC (SCV000637825.4 - Invitae)
BP4
No significant splice impact predicted: SpliceAI - acceptor/donor loss/gain 0.00 varSEAK - likely no splice effect (delta -16.92%) MaxEntScan - delta -0.43 (4.4% variation)
Not Met criteria codes
PVS1
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
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
PS4
7 probands with insufficient evidence to determine if HDGC criteria fulfilled. Families have personal or family history of breast or gastric cancer with no pathology information available (SCV000637825.4 - Invitae)
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
BA1
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
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
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
PM5
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
PM2
Latino/admixed American MAF 0.0001447 (0.01%, 5/34,548 alleles, 0 homozygotes in gnomAD v2.1)
Approved on: 2023-08-17
Published on: 2023-08-17
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