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.808T>G (p.Ser270Ala)

CA294235

142011 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f736f74f-a045-4573-aa21-41c5dfa9dd12
Approved on: 2023-08-17
Published on: 2023-08-17

HGVS expressions

NM_004360.5:c.808T>G
NM_004360.5(CDH1):c.808T>G (p.Ser270Ala)
NC_000016.10:g.68810317T>G
CM000678.2:g.68810317T>G
NC_000016.9:g.68844220T>G
CM000678.1:g.68844220T>G
NC_000016.8:g.67401721T>G
NG_008021.1:g.78026T>G
ENST00000261769.10:c.808T>G
ENST00000261769.9:c.808T>G
ENST00000422392.6:c.808T>G
ENST00000561751.1:n.455-1367T>G
ENST00000562836.5:n.879T>G
ENST00000566510.5:c.652T>G
ENST00000566612.5:c.808T>G
ENST00000611625.4:c.808T>G
ENST00000612417.4:c.808T>G
ENST00000621016.4:c.808T>G
NM_004360.3:c.808T>G
NM_001317184.1:c.808T>G
NM_001317185.1:c.-808T>G
NM_001317186.1:c.-1012T>G
NM_004360.4:c.808T>G
NM_001317184.2:c.808T>G
NM_001317185.2:c.-808T>G
NM_001317186.2:c.-1012T>G
More

Benign

Met criteria codes 2
BA1 BS2
Not Met criteria codes 24
PS2 PS3 PS4 PS1 BP3 BP2 BP4 BP1 BP7 BP5 PVS1 PP1 PP4 PP3 PP2 PM6 PM2 PM5 PM4 PM3 PM1 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.808T>G (p.Ser270Ala) variant has a maximum subpopulation frequency of 0.002269 (0.2269%, 57 of 25124 alleles) in the European (Finnish) subpopulation of the gnomAD v2.1.1 cohort (BA1). This variant has also has been observed in more than 10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; SCV000185687.6, SCV000254832.8). In summary, this variant meets criteria to be classified as benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BS2.
Met criteria codes
BA1
gnomAD 2.1.1 = 57 of 25124 alleles (0.2269%) in in Finnish populations (>0.2%). gnomAD 3.1 = 26 of 10598 alleles (0.2453%) in Finnish populations (>0.2%).
BS2
PMID: 11705864 - Detected in 5 of 923 controls. SCV000185687.6 (Ambry) - 23 families that do not meet HDGC clinical criteria. SCV000254832.8 (Invitae) - 43 families without CDH1 phenotypes described.
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
PMID: 27582386 - Exhibits strong adhesion, although a bit lower than WT, but cannot be activated by stimuli.
Exhibits strong adhesion, although a bit lower than WT, but cannot be activated by stimuli. PubMed:27582386
PS4
PMID: 11705864 - 2 diffuse gastric cancer cases, but no ages provided. PMID: 26898890 - 1 breast/ovarian cancer, no pathology provided. PMID: 30333958 - 2 breast/ovarian cancer, no pathology provided. Ambry - none of the 23 families provided meets criteria (additional data for 70 probands could be made available).
PS1
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
VarSEAK - No splicing effect. SpliceAI - Donor Gain: score 0.03 at 12 bp.
BP1
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
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
VarSEAK - No splicing effect. SpliceAI - Donor Gain: score 0.03 at 12 bp.
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
PM2
gnomAD 2.1.1 = 57 of 25124 alleles (0.2269%) in Finnish populations >0.2% and 9 of 7222 alleles (0.1246%) in others >0.1% and 59 of 129148 allelles (0.04568%) in Non-Finnish Europeans. gnomAD 3.1 = 26 of 10598 alleles (0.2453%) in Finnish populations and 25 of 68004 (0.03676%) in Non-Finnish Europeans.
PM5
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
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Exhibits strong adhesion, although a bit lower than WT, but cannot be activated by stimuli. PubMed:27582386
BS1
gnomAD 2.1.1 = 57 of 25124 alleles (0.2269%) in Finnish populations >0.2% and 9 of 7222 alleles (0.1246%) in others >0.1% and 59 of 129148 allelles (0.04568%) in Non-Finnish Europeans. gnomAD 3.1 = 26 of 10598 alleles (0.2453%) in Finnish populations and 25 of 68004 (0.03676%) in Non-Finnish Europeans.
Curation History
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