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_004360.4(CDH1):c.1085delT (p.Val362Glyfs)

CA658658486

483264 (ClinVar)

Gene: CDH1 (HGNC:999)
Condition: CDH1-related diffuse gastric and lobular breast cancer (MONDO:0007648)
Inheritance Mode: Autosomal dominant inheritance
UUID: c5d03db0-c5d6-426b-9059-585ca0cccb44
Approved on: 2018-11-21
Published on: 2018-12-07

HGVS expressions

NM_004360.4(CDH1):c.1085delT (p.Val362Glyfs)
NM_004360.4:c.1085delT
NC_000016.10:g.68812211del
CM000678.2:g.68812211del
NC_000016.9:g.68846114del
CM000678.1:g.68846114del
NC_000016.8:g.67403615del
NG_008021.1:g.79920del
ENST00000261769.10:c.1085del
ENST00000261769.9:c.1085del
ENST00000422392.6:c.1085del
ENST00000561751.1:n.707del
ENST00000562836.5:n.1156del
ENST00000565810.1:n.129del
ENST00000566510.5:c.929del
ENST00000566612.5:c.1085del
ENST00000611625.4:c.1085del
ENST00000612417.4:c.1085del
ENST00000621016.4:c.1085del
NM_004360.3:c.1085del
NM_001317184.1:c.1085del
NM_001317185.1:c.-531del
NM_001317186.1:c.-735del
NM_004360.4:c.1085del
NM_004360.5:c.1085del
NM_001317184.2:c.1085del
NM_001317185.2:c.-531del
NM_001317186.2:c.-735del
NM_004360.5(CDH1):c.1085del (p.Val362fs)
More

Pathogenic

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

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.1085delT (p.Val362Glyfs*31) 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; SCV000669065.1). 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.
Met criteria codes
PM2_Supporting
Absent in gnomAD.
PVS1
Frameshift causing CDH1 truncation. Truncating mutations downstream of this mutation. CDH1 has significant pNull score in ExAC.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Supporting
gastric cancer observed in proband and sister
Not Met criteria codes
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
Absent in gnomAD.
PP2
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
Although gastric cancer observed in sister, no segregation data for variant is available.
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
Variant causes truncation/protein length change.
PM6
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
Absent in gnomAD.
BS4
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
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
BP1
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
BP3
Variant causes truncation/protein length change.
Curation History
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