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]

Variant: NM_004360.5(CDH1):c.1170C>T (p.Asn390=)

CA187687

184069 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a4729f21-64a3-4581-a371-d3e87051f5fb
Approved on: 2023-09-25
Published on: 2023-09-27

HGVS expressions

NM_004360.5:c.1170C>T
NM_004360.5(CDH1):c.1170C>T (p.Asn390=)
NC_000016.10:g.68813345C>T
CM000678.2:g.68813345C>T
NC_000016.9:g.68847248C>T
CM000678.1:g.68847248C>T
NC_000016.8:g.67404749C>T
NG_008021.1:g.81054C>T
ENST00000261769.10:c.1170C>T
ENST00000261769.9:c.1170C>T
ENST00000422392.6:c.1137+1082C>T
ENST00000562836.5:n.1241C>T
ENST00000565810.1:n.214C>T
ENST00000566510.5:c.1014C>T
ENST00000566612.5:c.1170C>T
ENST00000611625.4:c.1170C>T
ENST00000612417.4:c.1170C>T
ENST00000621016.4:c.1170C>T
NM_004360.3:c.1170C>T
NM_001317184.1:c.1137+1082C>T
NM_001317185.1:c.-446C>T
NM_001317186.1:c.-650C>T
NM_004360.4:c.1170C>T
NM_001317184.2:c.1137+1082C>T
NM_001317185.2:c.-446C>T
NM_001317186.2:c.-650C>T
More

Likely Benign

Met criteria codes 3
BS2 BP4 BP7
Not Met criteria codes 3
BA1 PS4 BS1

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.1170C>T (p.Asn390=) variant results in a synonymous change in exon 9 of CDH1. This is a silent variant that occurs at a position that is not highly conserved and for which splicing predictors do not suggest an impact on splicing (BP4, BP7). This variant is absent from the gnomAD population database v3.1.2. This variant was identified in 70 individuals without DGC, LBC, SRC tumours and whose families do not suggest HDGC (BS2; PMID: 30287823, 36436516, and internal laboratory contributors). In summary, this variant is classified as likely benign based on ACMG/AMP criteria applied as likely benign specified by the CDH1 Variant Curation Expert Panel: BS2, BP4, BP7.
Met criteria codes
BS2
This variant was identified in more than 70 individuals not meeting IGCLC criteria for HDGC (PMID: 30287823, 36436516; and internal laboratory data). This variant was also found in 1 individual with LBC in 60s and 3 individuals with a FHx of gastric cancer (internal laboratory data).
BP4
This variant is not predicted to impact splicing.
BP7
This is a silent variant for which splicing predictors do not suggest an impact on splicing at a position that is not highly conserved.
Not Met criteria codes
BA1
This variant was observed in 1 of 251,478 alleles (3.976x10-6) in gnomAD v2.1.1 and is absent from gnomAD v3.1.2
PS4
This variant was identified in more than 70 individuals not meeting IGCLC criteria for HDGC (PMID: 30287823, 36436516; and internal laboratory data). This variant was also found in 1 individual with LBC in 60s and 3 individuals with a FHx of gastric cancer (internal laboratory data).
BS1
This variant was observed in 1 of 251,478 alleles (3.976x10-6) in gnomAD v2.1.1 and is absent from gnomAD v3.1.2
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.