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.1613A>T (p.Asp538Val)

CA338255

216589 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7a7009f6-789d-458a-a313-c7508dc251da

HGVS expressions

NM_004360.5:c.1613A>T
NM_004360.5(CDH1):c.1613A>T (p.Asp538Val)
NC_000016.10:g.68819327A>T
CM000678.2:g.68819327A>T
NC_000016.9:g.68853230A>T
CM000678.1:g.68853230A>T
NC_000016.8:g.67410731A>T
NG_008021.1:g.87036A>T
ENST00000261769.10:c.1613A>T
ENST00000261769.9:c.1613A>T
ENST00000422392.6:c.1430A>T
ENST00000562836.5:n.1684A>T
ENST00000566510.5:c.*279A>T
ENST00000566612.5:c.1566-2674A>T
ENST00000611625.4:c.1676A>T
ENST00000612417.4:c.1613A>T
ENST00000621016.4:c.1613A>T
NM_004360.3:c.1613A>T
NM_001317184.1:c.1430A>T
NM_001317185.1:c.65A>T
NM_001317186.1:c.-254-2674A>T
NM_004360.4:c.1613A>T
NM_001317184.2:c.1430A>T
NM_001317185.2:c.65A>T
NM_001317186.2:c.-254-2674A>T

Uncertain Significance

Met criteria codes 2
PM2_Supporting PS4_Moderate
Not Met criteria codes 24
PS3 PS2 PS1 BA1 PP4 PP3 PP2 PP1 PM4 PM5 PM3 PM1 PM6 PVS1 BS2 BS3 BS4 BS1 BP4 BP1 BP3 BP2 BP5 BP7

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.1613A>T (p.Asp538Val) variant is absent in the gnomAD cohort (PM2_Supporting). This variant has been reported in at least two families meeting HDGC clinical criteria (PS4_Moderate; SCV000254814.3). In summary, this variant meets criteria to be classified as a variant of uncertain significance based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting, PS4_Moderate.
Met criteria codes
PM2_Supporting
Absent in all population databases
PS4_Moderate
This variant has been reported in at least two families meeting HDGC clinical criteria (SCV000254814.3). Internal lab contributor: Gastric cancer dx @ 40s, pathology not specified. No reported FHx of cancer (Not Meet). SCV000254814.3: Proband #1: male with diffuse gastric cancer by 50s. No family history. (Not Meet) Proband #2: male with metastatic gastric cancer at 30s. FHx of gastric cancer. (Meet) Proband #3: female with diffuse gastric cancer at late 30s (Meet).
Not Met criteria codes
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
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
PP3
In silico splicing predictors (SSF, MaxEnt, NNSPLICE, GeneSplicer) predict no splicing effect.
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
2 meioses
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
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
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
BP3
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
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
Approved on: 2023-08-21
Published on: 2023-08-21
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