The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • 'cspec' property is found but contains no ID!

  • See Evidence submitted by expert panel for details.

Variant: NM_004360.5(CDH1):c.164-4G>A

CA192317

185577 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
UUID: e8ebbd96-aa4e-4e41-8cea-da0f5bf5f9f0
Approved on: 2023-08-02
Published on: 2023-08-02

HGVS expressions

NM_004360.5:c.164-4G>A
NM_004360.5(CDH1):c.164-4G>A
NC_000016.10:g.68801666G>A
CM000678.2:g.68801666G>A
NC_000016.9:g.68835569G>A
CM000678.1:g.68835569G>A
NC_000016.8:g.67393070G>A
NG_008021.1:g.69375G>A
ENST00000261769.10:c.164-4G>A
ENST00000261769.9:c.164-4G>A
ENST00000422392.6:c.164-4G>A
ENST00000562836.5:n.235-4G>A
ENST00000564676.5:n.446-4G>A
ENST00000564745.1:n.159-4G>A
ENST00000566510.5:c.164-4G>A
ENST00000566612.5:c.164-4G>A
ENST00000611625.4:c.164-4G>A
ENST00000612417.4:c.164-4G>A
ENST00000621016.4:c.164-4G>A
NM_004360.3:c.164-4G>A
NM_001317184.1:c.164-4G>A
NM_001317185.1:c.-1452-4G>A
NM_001317186.1:c.-1656-4G>A
NM_004360.4:c.164-4G>A
NM_001317184.2:c.164-4G>A
NM_001317185.2:c.-1452-4G>A
NM_001317186.2:c.-1656-4G>A
More

Likely Benign

Met criteria codes 3
BS2 BP4 PM2_Supporting
Not Met criteria codes 23
BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP1 PS2 PS4 PS3 PS1 PVS1 BA1 PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.164-4G>A (NM_004360.5) variant in CDH1 occurs in the splice donor region of intron 2. This variant has been observed in more than 10 individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; Ambry, GeneDx, Invitae). This variant occurs in one in 251,376 alleles in gnomAD 2.1.1 (less than one out of 100,000), within the European Non-Finnish population (one in 113,662 alleles) PM2_Supporting. In silico splice site predictors suggest that this variant does not impact splicing (BP4). However, splicing has not been assessed by in vitro assays. In summary, this variant meets the criteria to be classified as likely benign for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PM2_Supporting, BS2, BP4. (CDH1 VCEP specifications version 3.1; 04/24/2023)
Met criteria codes
BS2
This variant has been observed in 12 heterozygous individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; Ambry, GeneDx, Invitae). Note that this includes one individual with colorectal cancer and family history of gastric cancer NOS and one individual whose personal cancer history is not known.
BP4
This variant is not predicted to impact splicing.
PM2_Supporting
This variant occurs in one in 251,376 alleles in gnomAD 2.1.1 (less than one out of 100,000), within the European Non-Finnish population (one in 113,662 alleles) PM2_Supporting.
Not Met criteria codes
BS4
Not available.
BS3
Functional studies have not been reported for this variant.
BS1
This variant occurs in one in 251,376 alleles in gnomAD (GRCh37), within the European Non-Finnish population (one in 113,662 alleles).
BP5
To our knowledge, this variant has not been reported in an individual with an alternate molecular basis for disease.
BP7
BP7 does not apply to this variant.
BP2
To our knowledge, this variant has not been reported in cis or trans with a known pathogenic variant.
BP3
BP3 does not apply to CDH1.
BP1
BP1 does not apply to CDH1.
PS2
To our knowledge, this variant has not been reported as de novo.
PS4
This variant was identified in nine individuals without DGC, SRC tumours, LBC and whose families do not suggest HDGC (Ambry, GeneDx, Invitae). Note that this includes one individual with colorectal cancer and one reported gastric cancer NOS in the family (GeneDx).
PS3
Functional studies have not been reported for this variant.
PS1
PS1 does not apply to this variant.
PVS1
PVS1 does not apply to this variant.
BA1
This variant occurs in one in 251,376 alleles in gnomAD (GRCh37), within the European Non-Finnish population (one in 113,662 alleles).
PP4
PP4 does not apply to CDH1.
PP1
Not available.
PP3
This variant is not predicted to impact splicing.
PP2
PP2 does not apply to CDH1.
PM6
To our knowledge, this variant has not been reported as de novo.
PM3
PM3 does not apply to CDH1.
PM1
PM1 does not apply to CDH1.
PM4
PM4 does not apply to this variant.
PM5
PM5 does not apply to CDH1.
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.