Evidence Repository - Clinical Genome Resources

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_004360.4(CDH1):c.2131C>G (p.Leu711Val)

CA121988

12231 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 57c42482-7dfe-418f-9374-f3562e757ad4

Approved on: 2023-08-18

Published on: 2023-08-18

HGVS expressions

NM_004360.4:c.2131C>G

NM_004360.4(CDH1):c.2131C>G (p.Leu711Val)

NC_000016.10:g.68823593C>G

CM000678.2:g.68823593C>G

NC_000016.9:g.68857496C>G

CM000678.1:g.68857496C>G

NC_000016.8:g.67414997C>G

NG_008021.1:g.91302C>G

ENST00000261769.10:c.2131C>G

ENST00000261769.9:c.2131C>G

ENST00000422392.6:c.1948C>G

ENST00000562118.1:n.349C>G

ENST00000562836.5:n.2202C>G

ENST00000566510.5:c.*797C>G

ENST00000566612.5:c.*371C>G

ENST00000611625.4:c.2194C>G

ENST00000612417.4:c.1830+1474C>G

ENST00000621016.4:c.1865+1439C>G

NM_004360.3:c.2131C>G

NM_001317184.1:c.1948C>G

NM_001317185.1:c.583C>G

NM_001317186.1:c.166C>G

NM_004360.5:c.2131C>G

NM_001317184.2:c.1948C>G

NM_001317185.2:c.583C>G

NM_001317186.2:c.166C>G

NM_004360.5(CDH1):c.2131C>G (p.Leu711Val)

Likely Benign

BS2 PM2_Supporting

BS3 BS4 BS1 BP7 BP5 BP3 BP2 BP4 BP1 PS2 PS1 PS3 PS4 BA1 PP4 PP3 PP2 PP1 PM6 PM5 PM1 PM4 PM3 PVS1

Evidence Links 0

Expert Panel

CDH1 VCEP

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.2131C>G variant is <1/50,000 alleles (0.002%, 2/128,916 alleles) in the non-Finnish European subpopulation (PM2_Supporting; http://gnomad.broadinstitute.org). The 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). Use of the Bayesian point system for this variant with conflicting evidence. 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): PM2_Supporting, BS2.

BS2

11 probands that do not meet HDGC clinical criteria (SCV000185421.6). 7 families that do not meet HDGC clinical criteria (SCV000329234.7). 14 probands (and families) that do not meet clinical criteria for HDGC (SCV000254818.5).

PM2_Supporting

<1/50,000 alleles in a gnomAD subpopulation. Allele frequency is 0.00001551 (0.002%, 2/128,916 alleles) in non-Finnish European subpopulation - gnomAD v2.1.1.

BS3