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.2165-1G>C

CA396469209

532459 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
UUID: f5c0b414-5677-4009-9634-78b75edf3e17
Approved on: 2023-08-24
Published on: 2023-08-24

HGVS expressions

NM_004360.5:c.2165-1G>C
NM_004360.5(CDH1):c.2165-1G>C
NC_000016.10:g.68828173G>C
CM000678.2:g.68828173G>C
NC_000016.9:g.68862076G>C
CM000678.1:g.68862076G>C
NC_000016.8:g.67419577G>C
NG_008021.1:g.95882G>C
ENST00000261769.10:c.2165-1G>C
ENST00000261769.9:c.2165-1G>C
ENST00000422392.6:c.1982-1G>C
ENST00000562118.1:n.383-1G>C
ENST00000562836.5:n.2236-1G>C
ENST00000566510.5:c.*831-1G>C
ENST00000566612.5:c.*405-1G>C
ENST00000611625.4:c.2228-1G>C
ENST00000612417.4:c.1853+1619G>C
ENST00000621016.4:c.1865+6019G>C
NM_004360.3:c.2165-1G>C
NM_001317184.1:c.1982-1G>C
NM_001317185.1:c.617-1G>C
NM_001317186.1:c.200-1G>C
NM_004360.4:c.2165-1G>C
NM_001317184.2:c.1982-1G>C
NM_001317185.2:c.617-1G>C
NM_001317186.2:c.200-1G>C
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Likely Pathogenic

Met criteria codes 4
PM5_Supporting PVS1_Strong PM2_Supporting PS4_Supporting
Not Met criteria codes 22
PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM6 PM1 PM4 PM3 BA1 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2

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.2165-1G>C variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_strong, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). The variant has been reported in one proband meeting clinical criteria for HDGC (PS4_supporting; Ambry). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_strong, PS4_supporting, PM2_supporting, PM5_Supporting.
Met criteria codes
PM5_Supporting
Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
PVS1_Strong
In the canonical acceptor site of intron 13, predicted to activate a cryptic acceptor site in exon 14 leading to 34 bp deletion and a frameshift. Expected to undergo NMD
PM2_Supporting
Absent in gnomAD v2.1 in a region of sufficient coverage
PS4_Supporting
One proband meets HDGC clinical guidelines (Ambry). 5 families with insufficient evidence to meet HDGC clinical guidelines (SCV000760818.4 and internal laboratory contributor).
Not Met criteria codes
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
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
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
PM6
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
PM3
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
BS2
1 individual w/o DCG, SRC tumors, or LBC & whose family do not suggest HDGC
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
BS1
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
BP5
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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