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]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_001317186.2:c.-547G>A

CA288025

127909 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8faf113f-6435-4260-a800-624a3fa41581
Approved on: 2023-08-03
Published on: 2023-08-03

HGVS expressions

NM_001317186.2:c.-547G>A
NC_000016.10:g.68813448G>A
CM000678.2:g.68813448G>A
NC_000016.9:g.68847351G>A
CM000678.1:g.68847351G>A
NC_000016.8:g.67404852G>A
NG_008021.1:g.81157G>A
ENST00000261769.10:c.1273G>A
ENST00000261769.9:c.1273G>A
ENST00000422392.6:c.1137+1185G>A
ENST00000562836.5:n.1344G>A
ENST00000566510.5:c.1117G>A
ENST00000566612.5:c.1273G>A
ENST00000611625.4:c.1273G>A
ENST00000612417.4:c.1273G>A
ENST00000621016.4:c.1273G>A
NM_004360.3:c.1273G>A
NM_001317184.1:c.1137+1185G>A
NM_001317185.1:c.-343G>A
NM_001317186.1:c.-547G>A
NM_004360.4:c.1273G>A
NM_004360.5:c.1273G>A
NM_001317184.2:c.1137+1185G>A
NM_001317185.2:c.-343G>A
NM_004360.5(CDH1):c.1273G>A (p.Val425Ile)
More

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 12
PM6 BA1 BS3 BS4 BS1 BP5 BP2 PS3 PS2 PS4 PP1 PP3

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.1273G>A (p.Val425Ile) variant results in a conservative missense change in the Cadherin 3 domain of CDH1. This variant was observed in 6 in 152,140 alleles in the gnomAD v3.1.2 population database. This variant was observed in a proband with oral clefting (PMID:27227907). However, this variants has also been observed in more than 10 individuals without GC, DGC, gastric SRC tumours or LBC and whose families do not suggest HDGC (BS2). 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; 05/22/2023)
Met criteria codes
BS2
This variant has been identified in 185 families without HDGC. This variant was also identified in two probands with ILC in 40s and three families with a history of unspecified gastric cancer.
Not Met criteria codes
PM6
To our knowledge, this variant has not been reported in a proband meeting HDGC criteria.
BA1
This variant was identified in 6 of 152,140 alleles in gnomAD v3.1.2, at a maximum frequency of 0.058% (3 of 5,190 alleles) in the East Asian subpopulation.
BS3
To our knowledge, splicing studies for this variant have not been reported.
BS4
To our knowledge, this variant has not been shown to segregate in a family with HDGC.
BS1
This variant was identified in 6 of 152,140 alleles in gnomAD v3.1.2, at a maximum frequency of 0.058% (3 of 5,190 alleles) in the East Asian subpopulation.
BP5
To our knowledge, this variant has not been reported in a family with HDGC and an alternate molecular basis for disease.
BP2
To our knowledge, this variant has not been reported in a family with HDGC with a known pathogenic variant in CDH1.
PS3
To our knowledge, splicing studies for this variant have not been reported.
PS2
To our knowledge, this variant has not been reported in a proband meeting HDGC criteria.
PS4
This variant has been identified in 185 families without HDGC. This variant was also identified in two probands with ILC in 40s and three families with a history of unspecified gastric cancer.
PP1
To our knowledge, this variant has not been shown to segregate in a family with HDGC.
PP3
This variant is not predicted to alter splicing. PP3 is not applicable for protein predictions for CDH1.
Curation History
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