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Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).

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Criteria Specification: CSpec Registry PDF

Variant: NM_004360.4(CDH1):c.59G>A (p.Trp20Ter)

CA280996

12239 (ClinVar)

Gene: CDH1
Condition: hereditary diffuse gastric cancer
Inheritance Mode: Autosomal dominant inheritance

HGVS expressions

NM_004360.4:c.59G>A
NM_004360.4(CDH1):c.59G>A (p.Trp20Ter)
NC_000016.10:g.68738307G>A
CM000678.2:g.68738307G>A
NC_000016.9:g.68772210G>A
CM000678.1:g.68772210G>A
NC_000016.8:g.67329711G>A
NG_008021.1:g.6016G>A
NM_004360.3:c.59G>A
NM_001317184.1:c.59G>A
NM_001317185.1:c.-1557G>A
NM_001317186.1:c.-1761G>A
NM_004360.5:c.59G>A
ENST00000261769.9:c.59G>A
ENST00000422392.6:c.59G>A
ENST00000566510.5:c.59G>A
ENST00000566612.5:c.59G>A
ENST00000611625.4:c.59G>A
ENST00000612417.4:c.59G>A
ENST00000621016.4:c.59G>A

Pathogenic

Met criteria codes 3
PM2 PVS1 PS4_Moderate
Unmet criteria codes 16
PP3 PP1 PM6 PM4 BA1 BS2 BS1 BS3 BS4 BP7 BP5 BP4 BP2 PS1 PS3 PS2

Expert Panel

Evidence Links 3

Evidence submitted by expert panel
CDH1 VCEP
The c.59G>A (p.Trp20*) variant is predicted to result in a premature stop codon in exon 2 that leads to a truncated or absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2; http://gnomad.broadinstitute.org). This variant has been reported in at least two families meeting HDGC clinical criteria (PS4_Moderate; PMID: 10072428, 26182300). 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: PVS1, PM2, PS4_Moderate.
Met criteria codes
PM2
Allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.
PVS1
This variant is predicted to result in a premature stop codon in exon 2.
PS4_Moderate
This variant was identified in two families meeting IGCLC criteria for HDGC (PMID: 10072428, 26182300).

Unmet criteria codes
PP3
Not applicable.
PP1
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
PM4
Not applicable.
BA1
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
BS1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Not applicable.
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Not applicable.
BP2
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
PS3
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
Approved on: 2019-04-15
Published on: 2019-09-11
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