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]
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Variant: NM_004360.5(CDH1):c.1585A>G (p.Thr529Ala)

CA347984

220445 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 88638813-b5f0-4f17-909e-934d558b33e5

HGVS expressions

NM_004360.5:c.1585A>G
NM_004360.5(CDH1):c.1585A>G (p.Thr529Ala)
NC_000016.10:g.68819299A>G
CM000678.2:g.68819299A>G
NC_000016.9:g.68853202A>G
CM000678.1:g.68853202A>G
NC_000016.8:g.67410703A>G
NG_008021.1:g.87008A>G
ENST00000261769.10:c.1585A>G
ENST00000261769.9:c.1585A>G
ENST00000422392.6:c.1402A>G
ENST00000562836.5:n.1656A>G
ENST00000566510.5:c.*251A>G
ENST00000566612.5:c.1566-2702A>G
ENST00000611625.4:c.1648A>G
ENST00000612417.4:c.1585A>G
ENST00000621016.4:c.1585A>G
NM_004360.3:c.1585A>G
NM_001317184.1:c.1402A>G
NM_001317185.1:c.37A>G
NM_001317186.1:c.-254-2702A>G
NM_004360.4:c.1585A>G
NM_001317184.2:c.1402A>G
NM_001317185.2:c.37A>G
NM_001317186.2:c.-254-2702A>G

Uncertain Significance

Met criteria codes 1
BS2_Supporting
Not Met criteria codes 25
BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PVS1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM2 BA1 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.1585A>G (NM_004360.5) variant in CDH1 is a missense variant predicted to predicted to cause substitution of Thr by Ala at amino acid 529 (p.Thr529Ala). This variant has been observed in more than 3 heterozygous individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2_Supporting; PMID: 30287823, Ambry, Invitae). In summary, this variant is classified as uncertain significance for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: BS2_Supporting. (CDH1 VCEP specifications version 3.1; 04/24/2023)
Met criteria codes
BS2_Supporting
This variant has been observed in more than 3 heterozygous individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2_supporting; PMID: 30287823, Ambry, Invitae).
Not Met criteria codes
BS4
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
6 of 18394 alleles in East Asian population
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
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
PVS1
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
1 family reported to meet criteria in PMID: 32426482 but details were not provided. Three tested individuals with family history of stomach cancer NOS in 1 individual, not meeting HDGC criteria
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
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
6 of 18394 alleles in East Asian population
BA1
6 of 18394 alleles in East Asian population
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
T529P and T529I are VUS
Approved on: 2023-08-02
Published on: 2023-08-02
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