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]
Link to SEPIO compliant JSON-LD document

Variant: NM_004360.5(CDH1):c.150C>A (p.Arg50=)

CA10583402

239883 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 92f144f5-1369-44fc-9593-e69ef87fed36
Approved on: 2023-08-18
Published on: 2023-08-18

HGVS expressions

NM_004360.5:c.150C>A
NM_004360.5(CDH1):c.150C>A (p.Arg50=)
NC_000016.10:g.68738398C>A
CM000678.2:g.68738398C>A
NC_000016.9:g.68772301C>A
CM000678.1:g.68772301C>A
NC_000016.8:g.67329802C>A
NG_008021.1:g.6107C>A
ENST00000261769.10:c.150C>A
ENST00000261769.9:c.150C>A
ENST00000422392.6:c.150C>A
ENST00000566510.5:c.150C>A
ENST00000566612.5:c.150C>A
ENST00000611625.4:c.150C>A
ENST00000612417.4:c.150C>A
ENST00000621016.4:c.150C>A
NM_004360.3:c.150C>A
NM_001317184.1:c.150C>A
NM_001317185.1:c.-1466C>A
NM_001317186.1:c.-1670C>A
NM_004360.4:c.150C>A
NM_001317184.2:c.150C>A
NM_001317185.2:c.-1466C>A
NM_001317186.2:c.-1670C>A

Likely Benign

Met criteria codes 4
BS2 BP7 BP4 PM2_Supporting
Not Met criteria codes 22
PP4 PP1 PP3 PP2 PM6 BA1 PM5 PM3 PM1 PM4 BS4 BS3 BS1 PS1 PS2 PS4 PS3 BP5 BP2 BP3 BP1 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.150C>A (p.Arg50=) results in a synonymous amino acid change in exon 2. This variant was found in 1 of 153,336 alleles in gnomAD (0.00001) (PM2_Supporting; http://gnomad.broadinstitute.org). However, This variant has also been observed in more than 10 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000665066.2; SCV000288437.6; SCV000976762.1). This variant occurs at a position that is poorly conserved and multiple computational tools predict that this variant does not impact splicing (BP4, BP7). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2, BP4, BP7, PM2_Supporting.
Met criteria codes
BS2
This variant was observed in 30 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (Ambry, GeneDx, Invitae).
BP7
This position is not highly conserved.
BP4
Multiple computational tools predict that this variant does not impact splicing.
PM2_Supporting
This variant was found in 1 of 153,336 alleles in gnomAD (0.00001).
Not Met criteria codes
PP4
PP4 does not apply to CDH1.
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
PP2 does not apply to CDH1.
PM6
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
PM5
PM5 does not apply to CDH1.
PM3
PM3 does not apply to CDH1.
PM1
PM1 does not apply to CDH1.
PM4
PM4 does not apply to this variant.
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
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
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
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
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.
PVS1
PVS1 does not apply to this variant.
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.