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]
  • See Evidence submitted by expert panel for details.

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

CA396457824

428618 (ClinVar)

Gene: CDH1
Condition: hereditary diffuse gastric cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ca028ce0-bd1d-431b-bc8a-5a093746c744
Approved on: 2019-06-18
Published on: 2019-09-11

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
More

Likely Pathogenic

Met criteria codes 3
PM2 PS4_Moderate PVS1_Strong
Not Met criteria codes 23
PP1 PP2 PP3 PP4 PS1 PS2 PS3 PM1 PM3 PM5 PM4 PM6 BA1 BP5 BP7 BP4 BP3 BP1 BP2 BS1 BS4 BS3 BS2

Evidence Links 0

Expert Panel

Criteria Specification Information

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). This variant is absent in the gnomAD cohort (PM2; 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: PVS1_strong, PM2, PS4_moderate.
Met criteria codes
PM2
Not observed in population databases.
PS4_Moderate
SCV000580690.3 (2 cases of gastric cancer in one family, one with signet ring features) SCV000637838.2 (Hereditary diffuse gastric cancer).
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.
Not Met criteria codes
PP1
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
PP3
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
PS1
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
PS3
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
PM5
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
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
BP7
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
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
BP2
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
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
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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