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_004360.5(CDH1):c.2329G>A (p.Asp777Asn)

CA157963

127922 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a72a576c-4686-471f-808d-5e7d66cf6f15

HGVS expressions

NM_004360.5:c.2329G>A
NM_004360.5(CDH1):c.2329G>A (p.Asp777Asn)
NC_000016.10:g.68829687G>A
CM000678.2:g.68829687G>A
NC_000016.9:g.68863590G>A
CM000678.1:g.68863590G>A
NC_000016.8:g.67421091G>A
NG_008021.1:g.97396G>A
ENST00000261769.10:c.2329G>A
ENST00000261769.9:c.2329G>A
ENST00000422392.6:c.2146G>A
ENST00000562118.1:n.547G>A
ENST00000562836.5:n.2400G>A
ENST00000566510.5:c.*995G>A
ENST00000566612.5:c.*569G>A
ENST00000611625.4:c.2392G>A
ENST00000612417.4:c.1853+3133G>A
ENST00000621016.4:c.1866-4516G>A
NM_004360.3:c.2329G>A
NM_001317184.1:c.2146G>A
NM_001317185.1:c.781G>A
NM_001317186.1:c.364G>A
NM_004360.4:c.2329G>A
NM_001317184.2:c.2146G>A
NM_001317185.2:c.781G>A
NM_001317186.2:c.364G>A

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS4 PS1 BA1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM5 PM6 PM2 PVS1

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.2329G>A (p.Asp777Asn) missense variant has a frequency of 0.0001202 (34 of 282,830) in the gnomAD v2.1.1 cohort, with a maximum non-founder allele frequency of 0.0002400 (31 of 129,162) in the non-Finnish European subpopulation (http://gnomad.broadinstitute.org). This variant has been observed in >100 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000149760.14, SCV000261509.8, PMIDs: 29522266, 26534844, 26976419, 25142776, 24728327). In summary, the clinical significance of this variant is classified as Likely Benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2.
Met criteria codes
BS2
Variant has been observed in >100 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (SCV000149760.14, SCV000261509.8, PMIDs: 29522266, 26534844, 26976419, 25142776, 24728327).
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
Variant present in 34 of 282,830 alleles in gnomAD (0.0001202). Highest subpopulation is non-Finnish European with 31 of 129,162 alleles (0.0002400)
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
BP5
Ambry ClinVar submission (Accession: SCV000186559.5) states co-occurrence with a mutation in another gene that clearly explains a proband's phenotype. However, currently the only gene can apply BP5 is CTNNA1.
BP7
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
PS4
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
Variant present in 34 of 282,830 alleles in gnomAD (0.0001202). Highest subpopulation is non-Finnish European with 31 of 129,162 alleles (0.0002400)
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
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Variant present in 34 of 282,830 alleles in gnomAD (0.0001202). Highest subpopulation is non-Finnish European with 31 of 129,162 alleles (0.0002400)
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-08-17
Published on: 2023-08-17
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