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_004360.5(CDH1):c.1019C>T (p.Thr340Met)

CA165437

141450 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 242cf932-b735-47c6-93fa-ce7c4186cb51
Approved on: 2023-08-10
Published on: 2023-08-10

HGVS expressions

NM_004360.5:c.1019C>T
NM_004360.5(CDH1):c.1019C>T (p.Thr340Met)
NC_000016.10:g.68812145C>T
CM000678.2:g.68812145C>T
NC_000016.9:g.68846048C>T
CM000678.1:g.68846048C>T
NC_000016.8:g.67403549C>T
NG_008021.1:g.79854C>T
ENST00000261769.10:c.1019C>T
ENST00000261769.9:c.1019C>T
ENST00000422392.6:c.1019C>T
ENST00000561751.1:n.641C>T
ENST00000562836.5:n.1090C>T
ENST00000565810.1:n.63C>T
ENST00000566510.5:c.863C>T
ENST00000566612.5:c.1019C>T
ENST00000611625.4:c.1019C>T
ENST00000612417.4:c.1019C>T
ENST00000621016.4:c.1019C>T
NM_004360.3:c.1019C>T
NM_001317184.1:c.1019C>T
NM_001317185.1:c.-597C>T
NM_001317186.1:c.-801C>T
NM_004360.4:c.1019C>T
NM_001317184.2:c.1019C>T
NM_001317185.2:c.-597C>T
NM_001317186.2:c.-801C>T
More

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
BP7 BP5 BP2 BP3 BP4 BP1 PS2 PS3 PS4 PS1 PP1 PP4 PP3 PP2 PM6 PM2 PM5 PM1 PM3 PM4 BA1 PVS1 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.1019C>T (p.Thr340Met) missense variant has a frequency of 0.0123% in Africans (2 of 16256 alleles) in the gnomAD v2.1.1 cohort. This variant has been observed in ≥10 (14) individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000254803.10, SCV000184790.6). In summary, the clinical significance of this variant is classified as of likely benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2.
Met criteria codes
BS2
Observed in 14 individuals without HDGC phenotypes (SCV000254803.10, SCV000184790.6).
Not Met criteria codes
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
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
VarSEAK: No splicing effect. SpliceAI - Donor Loss: SCORE = 0.10 at 35 bp.
BP1
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
PS3
No published functional studies.
PS4
No probands meeting HDGC criteria in the literature.
PS1
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
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
VarSEAK: No splicing effect. Spliceai - Donor Loss: SCORE = 0.10 at 35 bp.
PP2
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
gnomAD 2.1.1 = 2 of 16256 alleles (0.0123%) in Africans. gnomAD 3.1 = 7 of 41410 (0.01695%) in Africans.
PM5
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
PM3
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
BA1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No published functional studies.
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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.