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

Variant: NM_004360.4(CDH1):c.531+1G>A

CA396457824

428618 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ca028ce0-bd1d-431b-bc8a-5a093746c744
Approved on: 2024-03-28
Published on: 2024-03-28

HGVS expressions

NM_004360.4:c.531+1G>A
NM_004360.4(CDH1):c.531+1G>A
NC_000016.10:g.68808568G>A
CM000678.2:g.68808568G>A
NC_000016.9:g.68842471G>A
CM000678.1:g.68842471G>A
NC_000016.8:g.67399972G>A
NG_008021.1:g.76277G>A
ENST00000261769.10:c.531+1G>A
ENST00000261769.9:c.531+1G>A
ENST00000422392.6:c.531+1G>A
ENST00000561751.1:c.298+1G>A
ENST00000562836.5:n.602+1G>A
ENST00000564676.5:n.813+1G>A
ENST00000564745.1:n.526+1G>A
ENST00000566510.5:c.531+1G>A
ENST00000566612.5:c.531+1G>A
ENST00000567320.1:n.41+1G>A
ENST00000611625.4:c.531+1G>A
ENST00000612417.4:c.531+1G>A
ENST00000621016.4:c.531+1G>A
NM_004360.3:c.531+1G>A
NM_001317184.1:c.531+1G>A
NM_001317185.1:c.-1085+1G>A
NM_001317186.1:c.-1289+1G>A
NM_004360.5:c.531+1G>A
NM_001317184.2:c.531+1G>A
NM_001317185.2:c.-1085+1G>A
NM_001317186.2:c.-1289+1G>A
NM_004360.5(CDH1):c.531+1G>A

Likely Pathogenic

Met criteria codes 4
PVS1_Strong PS4_Moderate PM5_Supporting PM2_Supporting
Not Met criteria codes 22
BA1 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM4 PM1 PM3 PM6

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.531+1G>A variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least two family meeting HDGC clinical criteria (PS4_moderate; SCV000580690.3; SCV000637838.2). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_strong, PM2_Supporting, PS4_moderate, PM5_Supporting.
Met criteria codes
PVS1_Strong
As per CDH1 ClinGen guidelines, PVS1_strong is invoked for canonical splice variants. This site is invariant in all transcripts. Predicted in-frame exon 4 skipping (p.(Ala130_Gln177del), 48 aa, accounts for ~5.4% of protein). No RNA studies available. No other variants at this position or +2 position recorded in ClinVar.
PS4_Moderate
SCV000580690.3 (2 cases of gastric cancer in one family, one with signet ring features). SCV000637838.2 (2 cases GC, one confirmed DGC).
PM5_Supporting
Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
PM2_Supporting
Not observed in population databases.
Not Met criteria codes
BA1
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
BS4
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
BS2
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
BP5
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
BP2
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
PS3
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
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
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
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
PM3
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
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