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_004360.4(CDH1):c.286A>G (p.Ile96Val)

CA349520

220611 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d9039763-3145-4298-b468-da3967101df3

HGVS expressions

NM_004360.4:c.286A>G
NM_004360.4(CDH1):c.286A>G (p.Ile96Val)
NC_000016.10:g.68801792A>G
CM000678.2:g.68801792A>G
NC_000016.9:g.68835695A>G
CM000678.1:g.68835695A>G
NC_000016.8:g.67393196A>G
NG_008021.1:g.69501A>G
ENST00000261769.10:c.286A>G
ENST00000261769.9:c.286A>G
ENST00000422392.6:c.286A>G
ENST00000561751.1:n.53A>G
ENST00000562836.5:n.357A>G
ENST00000564676.5:n.568A>G
ENST00000564745.1:n.281A>G
ENST00000566510.5:c.286A>G
ENST00000566612.5:c.286A>G
ENST00000611625.4:c.286A>G
ENST00000612417.4:c.286A>G
ENST00000621016.4:c.286A>G
NM_004360.3:c.286A>G
NM_001317184.1:c.286A>G
NM_001317185.1:c.-1330A>G
NM_001317186.1:c.-1534A>G
NM_004360.5:c.286A>G
NM_001317184.2:c.286A>G
NM_001317185.2:c.-1330A>G
NM_001317186.2:c.-1534A>G
NM_004360.5(CDH1):c.286A>G (p.Ile96Val)

Benign

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

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.286A>G (p.Ile96Val) variant has an allele frequency of 0.00122 (0.12%, 41/33,578 alleles) in the Latino subpopulation of the gnomAD cohort (BS1). This variant has also been observed in >10 without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS1, BS2.
Met criteria codes
BS1
Frequency of 0.16% in ExAC, 0.12% in gnomAD
BS2
Observed in 42 individuals w/o a dx of HDGC.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Frequency of 0.16% in ExAC, 0.12% in Gnomad
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
1 homozygote in gnomAD
BP1
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
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
PP4
Reported in one Hispanic individual with HDGC
This variant was reported in one Hispanic proband with Diffuse gastric cancer at age 29 but no family history. Meets IGCLC criteria 3. PubMed:26182300
PP1
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
PP3
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
Frequency of 0.16% in ExAC, 0.12% in gnomAD
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Reported in one Hispanic individual with HDGC
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
PM4
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
PM5
Other variant at this position in Clinvar is VUS
Approved on: 2023-08-10
Published on: 2023-08-10
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