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.1363G>A (p.Ala455Thr)

CA396462787

481700 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0cbd5cfe-4faa-4a13-b3bd-990058040f71
Approved on: 2023-08-02
Published on: 2023-08-02

HGVS expressions

NM_004360.5:c.1363G>A
NM_004360.5(CDH1):c.1363G>A (p.Ala455Thr)
NC_000016.10:g.68815557G>A
CM000678.2:g.68815557G>A
NC_000016.9:g.68849460G>A
CM000678.1:g.68849460G>A
NC_000016.8:g.67406961G>A
NG_008021.1:g.83266G>A
ENST00000261769.10:c.1363G>A
ENST00000261769.9:c.1363G>A
ENST00000422392.6:c.1180G>A
ENST00000562836.5:n.1434G>A
ENST00000566510.5:c.*29G>A
ENST00000566612.5:c.1363G>A
ENST00000611625.4:c.1426G>A
ENST00000612417.4:c.1363G>A
ENST00000621016.4:c.1363G>A
NM_004360.3:c.1363G>A
NM_001317184.1:c.1180G>A
NM_001317185.1:c.-186G>A
NM_001317186.1:c.-457G>A
NM_004360.4:c.1363G>A
NM_001317184.2:c.1180G>A
NM_001317185.2:c.-186G>A
NM_001317186.2:c.-457G>A

Uncertain Significance

Met criteria codes 2
PM2_Supporting BS2_Supporting
Not Met criteria codes 24
BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PM6 PVS1 PS2 PS4 PS3 PS1 PM3 PM4 PM1 PM5 BA1 PP4 PP1 PP3 PP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.1363G>A (NM_004360.5) variant in CDH1 is a missense variant predicted to predicted to cause substitution of Ala by Thr at amino acid 455 (p.Ala455Thr). This variant was observed in more than three heterozygous individuals with no DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2_Supporting; Invitae, Ambry, GeneDx). This variant is absent from gnomAD 2.1.1 (PM2_Spporting). 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: PM2_Supporting, BS2_supporting. (CDH1 VCEP specifications version 3.1; 04/24/2023)
Met criteria codes
PM2_Supporting
This variant is absent in gnomAD v2.1.1 (PM2_Supporting).
BS2_Supporting
This variant has been observed in more than 3 heterozygous individuals with no GC, DGC, SRC tumours and whose families do not suggest HDGC (BS2_Supporting; Invitae, Ambry, GeneDx).
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
absent in gnomAD v2.1.1
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
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
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
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
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
NM_004360.5(CDH1):c.1363G>T (p.Ala455Ser) is VUS
BA1
absent in gnomAD v2.1.1
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
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