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]
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Variant: NM_004360.5(CDH1):c.2399G>A (p.Arg800His)

CA294379

142363 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: df17608e-32cd-47b7-8dab-62c2935b5bbe
Approved on: 2023-08-10
Published on: 2023-08-10

HGVS expressions

NM_004360.5:c.2399G>A
NM_004360.5(CDH1):c.2399G>A (p.Arg800His)
NC_000016.10:g.68829757G>A
CM000678.2:g.68829757G>A
NC_000016.9:g.68863660G>A
CM000678.1:g.68863660G>A
NC_000016.8:g.67421161G>A
NG_008021.1:g.97466G>A
ENST00000261769.10:c.2399G>A
ENST00000261769.9:c.2399G>A
ENST00000422392.6:c.2216G>A
ENST00000562118.1:n.617G>A
ENST00000562836.5:n.2470G>A
ENST00000566510.5:c.*1065G>A
ENST00000566612.5:c.*639G>A
ENST00000611625.4:c.2462G>A
ENST00000612417.4:c.1853+3203G>A
ENST00000621016.4:c.1866-4446G>A
NM_004360.3:c.2399G>A
NM_001317184.1:c.2216G>A
NM_001317185.1:c.851G>A
NM_001317186.1:c.434G>A
NM_004360.4:c.2399G>A
NM_001317184.2:c.2216G>A
NM_001317185.2:c.851G>A
NM_001317186.2:c.434G>A

Benign

Met criteria codes 2
BP2_Strong BS2
Not Met criteria codes 24
BA1 PVS1 BS4 BS3 BS1 BP3 BP4 BP1 BP5 BP7 PS4 PS2 PS3 PS1 PP1 PP4 PP3 PP2 PM3 PM1 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
The c.2399G>A (p.Arg800His) variant has an allele frequency of 0.00003 (0.003%, 1/30,614 alleles) in the South Asian gnomAD subpopulation (http://gnomad.broadinstitute.org). The variant has been seen in >10 individuals without DCG, SRC tumors, or LBC and whose families do not suggest HDGC (BS2; PMID: 26072394, SCV000186429.5, SCV000210876.13, SCV000254822.4). The variant has been identified in the homozygous state in an individual without personal and family history of DGC, LBC, or SRC tumors (BP2_Strong; SCV000186429.5). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP2_Strong.
Met criteria codes
BP2_Strong
Proband homozygous without meeting HDGC phenotype criteria (SCV000186429.5)
BS2
Variant seen in >10 (23) individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC (PMID: 26072394, SCV000186429.5, SCV000210876.13, SCV000254822.4).
Not Met criteria codes
BA1
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
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
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
PS4
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
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
No significant splicing alteration detected (MES, HSF)
PP2
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
>1/50,000 alleles in gnomAD subpopulations: global AF is 0.00002 (0.002%, 4/251,258 alleles). The maximum frequency is 0.00003 in South Asian (1/30,614 alleles) and Latino (1/34,588 alleles) subpopulations.
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