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.480_486delinsAGAATA (p.Ile161fs)

CA658658479

479524 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9b7f21ff-48e0-4483-9bac-0393271e0fbc
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.480_486delinsAGAATA
NM_004360.5(CDH1):c.480_486delinsAGAATA (p.Ile161fs)
NC_000016.10:g.68808516_68808522delinsAGAATA
CM000678.2:g.68808516_68808522delinsAGAATA
NC_000016.9:g.68842419_68842425delinsAGAATA
CM000678.1:g.68842419_68842425delinsAGAATA
NC_000016.8:g.67399920_67399926delinsAGAATA
NG_008021.1:g.76225_76231delinsAGAATA
ENST00000261769.10:c.480_486delinsAGAATA
ENST00000261769.9:c.480_486delinsAGAATA
ENST00000422392.6:c.480_486delinsAGAATA
ENST00000561751.1:n.247_253delinsAGAATA
ENST00000562836.5:n.551_557delinsAGAATA
ENST00000564676.5:n.762_768delinsAGAATA
ENST00000564745.1:n.475_481delinsAGAATA
ENST00000566510.5:c.480_486delinsAGAATA
ENST00000566612.5:c.480_486delinsAGAATA
ENST00000611625.4:c.480_486delinsAGAATA
ENST00000612417.4:c.480_486delinsAGAATA
ENST00000621016.4:c.480_486delinsAGAATA
NM_004360.3:c.480_486delinsAGAATA
NM_001317184.1:c.480_486delinsAGAATA
NM_001317185.1:c.-1136_-1130delinsAGAATA
NM_001317186.1:c.-1340_-1334delinsAGAATA
NM_004360.4:c.480_486delinsAGAATA
NM_001317184.2:c.480_486delinsAGAATA
NM_001317185.2:c.-1136_-1130delinsAGAATA
NM_001317186.2:c.-1340_-1334delinsAGAATA

Pathogenic

Met criteria codes 4
PVS1 PM2_Supporting PS4_Supporting PM5_Supporting
Not Met criteria codes 22
BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4

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.480_486delinsAGAATA p.(Ile161Glufs*54) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000661678.2). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.
Met criteria codes
PVS1
Frameshift in exon 4 and PTC created 54 amino acids downstream (Ile161Glufs*54) in exon 5 of 16, expected to undergo NMD.
PM2_Supporting
Absent in gnomAD v2.1.1, in a region of sufficient coverage
PS4_Supporting
One family that fulfils HDGC clinical criteria: obligate carrier with signet cell type gastric cancer diagnosed in 30s (Ambry - SCV000661678.2)
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
Not Met criteria codes
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
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
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
PS2
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
PS1
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
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
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
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