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.344C>T (p.Thr115Met)

CA293962

140878 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d24f25e0-35d1-41c7-aa8a-675f6fa2a9b8
Approved on: 2023-08-03
Published on: 2023-08-03

HGVS expressions

NM_004360.5:c.344C>T
NM_004360.5(CDH1):c.344C>T (p.Thr115Met)
NC_000016.10:g.68801850C>T
CM000678.2:g.68801850C>T
NC_000016.9:g.68835753C>T
CM000678.1:g.68835753C>T
NC_000016.8:g.67393254C>T
NG_008021.1:g.69559C>T
ENST00000261769.10:c.344C>T
ENST00000261769.9:c.344C>T
ENST00000422392.6:c.344C>T
ENST00000561751.1:n.111C>T
ENST00000562836.5:n.415C>T
ENST00000564676.5:n.626C>T
ENST00000564745.1:n.339C>T
ENST00000566510.5:c.344C>T
ENST00000566612.5:c.344C>T
ENST00000611625.4:c.344C>T
ENST00000612417.4:c.344C>T
ENST00000621016.4:c.344C>T
NM_004360.3:c.344C>T
NM_001317184.1:c.344C>T
NM_001317185.1:c.-1272C>T
NM_001317186.1:c.-1476C>T
NM_004360.4:c.344C>T
NM_001317184.2:c.344C>T
NM_001317185.2:c.-1272C>T
NM_001317186.2:c.-1476C>T

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
BP5 BP7 BP2 BP3 BP4 BP1 PS1 PS2 PS4 PS3 PP4 PP1 PP3 PP2 PVS1 BA1 PM5 PM3 PM1 PM4 PM6 PM2 BS4 BS3 BS1

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.344C>T (p.Thr115Met) missense variant has a maximum subpopulation frequency of 0.0097% in the gnomAD v2.1.1 cohort (http://gnomad.broadinstitute.org). This variant has been observed in over 75 probands not meeting HDGC phenotype criteria (BS2; SCV000254830.11, SCV000210896.16, SCV000183817.7). In summary, this variant meets criteria to be classified as Likely Benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 06/26/2023)
Met criteria codes
BS2
>75 probands/families not meeting HDGC criteria.
Not Met criteria codes
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Do not use protein based computational prediction models and BP4 is not applicable for missense variants.
BP1
Not applicable for CDH1.
PS1
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
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
This rule can only be applied to demonstrate splicing defects.
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
PP3 cannot be applied for canonical splice sites. PP3 code also does not apply to the last nucleotide of exon 3 (c.387G). Do not use protein-based computational prediction models for missense variants.
PP2
Not applicable for CDH1.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Maximum subpopulation frequency of 0.0097% in gnomAD v2.1.1
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
Not applicable for CDH1.
PM4
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
PM2
Maximum subpopulation frequency of 0.0097% in gnomAD v2.1.1
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
This rule can only be used to demonstrate lack of splicing and can only be applied to Synonymous, Intronic or Non-coding variants. BS3 may be downgraded based on quality of data.
BS1
Maximum subpopulation frequency of 0.0097% in gnomAD v2.1.1
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.