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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_004360.5(CDH1):c.61C>G (p.Leu21Val)

CA10580066

230175 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8d14ba7e-4b70-4457-a487-62b5bad7739f
Approved on: 2023-08-21
Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.61C>G
NM_004360.5(CDH1):c.61C>G (p.Leu21Val)
NC_000016.10:g.68738309C>G
CM000678.2:g.68738309C>G
NC_000016.9:g.68772212C>G
CM000678.1:g.68772212C>G
NC_000016.8:g.67329713C>G
NG_008021.1:g.6018C>G
ENST00000261769.10:c.61C>G
ENST00000261769.9:c.61C>G
ENST00000422392.6:c.61C>G
ENST00000566510.5:c.61C>G
ENST00000566612.5:c.61C>G
ENST00000611625.4:c.61C>G
ENST00000612417.4:c.61C>G
ENST00000621016.4:c.61C>G
NM_004360.3:c.61C>G
NM_001317184.1:c.61C>G
NM_001317185.1:c.-1555C>G
NM_001317186.1:c.-1759C>G
NM_004360.4:c.61C>G
NM_001317184.2:c.61C>G
NM_001317185.2:c.-1555C>G
NM_001317186.2:c.-1759C>G
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Uncertain Significance

Met criteria codes 1
BS2_Supporting
Not Met criteria codes 25
PM1 PM3 PM5 PM4 PM6 PM2 BA1 BS1 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7 PS1 PS2 PS3 PS4 PVS1 PP1 PP2 PP3 PP4

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.61C>G (p.Leu21Val) variant results in a non-synonymous amino acid change in exon 2. This variant is present in 5 of 188,446 alleles (0.00003) in gnomAD, present exclusively in the East Asian subpopulation with 5 of 12,882 alleles (0.00039). This variant has been observed in at least three individuals without DGC, SRC tumour or LBC and whose families do not suggest HDGC (BS2_supporting). In summary, the clinical significance of this variant is uncertain based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2_supporting.
Met criteria codes
BS2_Supporting
This variant was observed in nine individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (Ambry, GeneDx, Invitae).
Not Met criteria codes
PM1
PM1 does not apply to CDH1.
PM3
PM3 does not apply to CDH1.
PM5
PM5 does not apply to CDH1.
PM4
PM4 does not apply to this variant.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).
BA1
This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).
BS1
This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).
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
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
BP3 does not apply to CDH1.
BP1
BP1 does not apply to CDH1.
BP2
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
BP7 does not apply to this variant.
PS1
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
PS4
This variant was found in one individual with gastric cancer with diffuse features and a first-degree relative with gastric cancer (GeneDx). However, PS4 not meet since less than 30% reported individuals meet HDGC criteria.
PVS1
PVS1 does not apply to this variant.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
PP2 does not apply to CDH1.
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
PP4 does not apply to CDH1.
Curation History
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