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.1443del (p.Asn481fs)

CA658683954

491497 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 12091b2d-cd93-4041-be48-e1f93b317490
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.1443del
NM_004360.5(CDH1):c.1443del (p.Asn481fs)
NC_000016.10:g.68815637del
CM000678.2:g.68815637del
NC_000016.9:g.68849540del
CM000678.1:g.68849540del
NC_000016.8:g.67407041del
NG_008021.1:g.83346del
ENST00000261769.10:c.1443del
ENST00000261769.9:c.1443del
ENST00000422392.6:c.1260del
ENST00000562836.5:n.1514del
ENST00000566510.5:c.*109del
ENST00000566612.5:c.1443del
ENST00000611625.4:c.1506del
ENST00000612417.4:c.1443del
ENST00000621016.4:c.1443del
NM_004360.3:c.1443del
NM_001317184.1:c.1260del
NM_001317185.1:c.-106del
NM_001317186.1:c.-377del
NM_004360.4:c.1443del
NM_001317184.2:c.1260del
NM_001317185.2:c.-106del
NM_001317186.2:c.-377del
More

Pathogenic

Met criteria codes 3
PM5_Supporting PM2_Supporting PVS1
Not Met criteria codes 23
PS2 PS4 PS3 PS1 BP5 BP7 BP2 BP3 BP4 BP1 PP4 PP1 PP3 PP2 BA1 PM6 PM3 PM1 PM4 BS2 BS4 BS3 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.1443del (p.Asn481fs) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Met criteria codes
PM5_Supporting
Frameshift variant predicted to result in NMD and stop codon at aa 521
PM2_Supporting
Variant is not present in gnomAD
PVS1
Frameshift variant predicted to result in NMD and stop codon at aa 521
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Proband with unknown primary and family history of gastric cancer in mother and grandmother diagnosed at 40s and 70s, respectively (Not Met; no pathology available; SCV000689453.2)
PS3
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
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
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
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Variant is not present in gnomAD
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
Variant is not present in gnomAD
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.