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
  • 'cspec' property is found but contains no ID!
  • See Evidence submitted by expert panel for details.

Variant: NM_004360.5(CDH1):c.270G>A (p.Arg90=)

CA8129820

414048 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: af4a8259-777d-42cb-aea7-dfda3ec7bd6c
Approved on: 2023-08-02
Published on: 2023-08-02

HGVS expressions

NM_004360.5:c.270G>A
NM_004360.5(CDH1):c.270G>A (p.Arg90=)
NC_000016.10:g.68801776G>A
CM000678.2:g.68801776G>A
NC_000016.9:g.68835679G>A
CM000678.1:g.68835679G>A
NC_000016.8:g.67393180G>A
NG_008021.1:g.69485G>A
ENST00000261769.10:c.270G>A
ENST00000261769.9:c.270G>A
ENST00000422392.6:c.270G>A
ENST00000561751.1:n.37G>A
ENST00000562836.5:n.341G>A
ENST00000564676.5:n.552G>A
ENST00000564745.1:n.265G>A
ENST00000566510.5:c.270G>A
ENST00000566612.5:c.270G>A
ENST00000611625.4:c.270G>A
ENST00000612417.4:c.270G>A
ENST00000621016.4:c.270G>A
NM_004360.3:c.270G>A
NM_001317184.1:c.270G>A
NM_001317185.1:c.-1346G>A
NM_001317186.1:c.-1550G>A
NM_004360.4:c.270G>A
NM_001317184.2:c.270G>A
NM_001317185.2:c.-1346G>A
NM_001317186.2:c.-1550G>A

Likely Benign

Met criteria codes 4
BS2 BP4 BP7 PM2_Supporting
Not Met criteria codes 22
PVS1 BS4 BS3 BS1 BP2 BP3 BP1 BP5 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM6 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.270G>A variant (NM_004360.5) is a synonymous (silent) variant (p.Arg90=) that is not predicted by SpliceAI, varSEAK to impact splicing (BP4, BP7). This variant has been observed in more than 10 heterozygous individuals with no GC, DGC, SRC tumors and whose families do not suggest HDGC (BS2; Invitae, Ambry, GeneDX). The variant is 1 out of 251,334 alleles (less than 1 out of 100,000) in gnomAD 2.1.1 cohort (PM2_Supporting). In summary, this variant meets criteria to be classified as likely benign for DGLBCS based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2, BP4, BP7, PM2_Supporting. The CDH1 VCEP classified the variant with conflicting criteria to likely benign based on Bayesian points calculation. (CDH1 VCEP specifications version 3.1; 05/06/2022)
Met criteria codes
BS2
This variant has been observed in more than 10 heterozygous individuals with no GC, DGC, SRC tumors and whose families do not suggest HDGC (BS2; Invitae, Ambry, GeneDX).
BP4
The results from 2 in silico predictors, SpliceAI, varSEAK, suggest that the variant does not impact CHD1 function via altering splicing (BP4).
BP7
The NM_004360.5:c.270G>A (p.Arg90=) variant is a synonymous (silent) variant that is not predicted by SpliceAI, varSEAK to impact splicing. In addition, it occurs at a nucleotide that is not conserved (BP7).
PM2_Supporting
The variant is 1 out of 251,334 alleles (less than 1 out of 100,000) in gnomAD 2.1.1 cohort (PM2).
Not Met criteria codes
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 code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
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
BP1
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant identified in 3 probands with personal history of lobular breast cancer but otherwise not meeting 2020 HDGC genetic testing 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
BA1
1 6134
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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.