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.1174G>A (p.Val392Ile)

CA288019

127907 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
UUID: bd98b25e-474c-4452-882d-ca770a6c6389
Approved on: 2023-08-10
Published on: 2023-08-10

HGVS expressions

NM_004360.5:c.1174G>A
NM_004360.5(CDH1):c.1174G>A (p.Val392Ile)
NC_000016.10:g.68813349G>A
CM000678.2:g.68813349G>A
NC_000016.9:g.68847252G>A
CM000678.1:g.68847252G>A
NC_000016.8:g.67404753G>A
NG_008021.1:g.81058G>A
ENST00000261769.10:c.1174G>A
ENST00000261769.9:c.1174G>A
ENST00000422392.6:c.1137+1086G>A
ENST00000562836.5:n.1245G>A
ENST00000565810.1:n.218G>A
ENST00000566510.5:c.1018G>A
ENST00000566612.5:c.1174G>A
ENST00000611625.4:c.1174G>A
ENST00000612417.4:c.1174G>A
ENST00000621016.4:c.1174G>A
NM_004360.3:c.1174G>A
NM_001317184.1:c.1137+1086G>A
NM_001317185.1:c.-442G>A
NM_001317186.1:c.-646G>A
NM_004360.4:c.1174G>A
NM_001317184.2:c.1137+1086G>A
NM_001317185.2:c.-442G>A
NM_001317186.2:c.-646G>A
More

Likely Benign

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

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.1174G>A variant has been observed in >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; internal laboratory contributors). This variant was observed in trans with a known pathogenic CDH1 variant (phase unknown) and observed in the homozygous state in gnomAD v2.0.2 (BP2; internal laboratory contributor and gnomAD). Therefore, the clinical significance of this variant is likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP2.
Met criteria codes
BS2
9 probands that do not meet clinical criteria for HDGC (SCV000149744.10). 34 probands (and families) that do not meet clinical criteria for HDGC (SCV000218553.6). At least 17 probands that do not meet HDGC clinical criteria (SCV000665118.2).
BP2
A proband meets clinical criteria for HDGC whose condition can be explained by the presence of a pathogenic frameshift CDH1 variant (phase unknown; SCV000218553.6). The homozygote reported in the 'Other' subpopulation in gnomAD v2.0.2 is not present in gnomAD v2.1.1.
Not Met criteria codes
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
MAF <0.1%: gnomAD v2.0.2 South Asian AF = 0.00088 (27/30782 alleles) Total AF = 0.00015 (36/246242 alleles)
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
Observed in cases with pathogenic variants in ATM and BRCA2 (SCV000149744.10 - GeneDx), which are genes with overlapping phenotypes with CDH1.
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
PS4
One proband doesn't meet HDGC criteria (SCV000149744.10)
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
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
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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