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.1493A>C (p.Asp498Ala)

CA10577544

234528 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b16b8eee-01a1-4a10-b40c-0f1bf8dc18b7

HGVS expressions

NM_004360.5:c.1493A>C
NM_004360.5(CDH1):c.1493A>C (p.Asp498Ala)
NC_000016.10:g.68815687A>C
CM000678.2:g.68815687A>C
NC_000016.9:g.68849590A>C
CM000678.1:g.68849590A>C
NC_000016.8:g.67407091A>C
NG_008021.1:g.83396A>C
ENST00000261769.10:c.1493A>C
ENST00000261769.9:c.1493A>C
ENST00000422392.6:c.1310A>C
ENST00000562836.5:n.1564A>C
ENST00000566510.5:c.*159A>C
ENST00000566612.5:c.1493A>C
ENST00000611625.4:c.1556A>C
ENST00000612417.4:c.1493A>C
ENST00000621016.4:c.1493A>C
NM_004360.3:c.1493A>C
NM_001317184.1:c.1310A>C
NM_001317185.1:c.-56A>C
NM_001317186.1:c.-327A>C
NM_004360.4:c.1493A>C
NM_001317184.2:c.1310A>C
NM_001317185.2:c.-56A>C
NM_001317186.2:c.-327A>C

Likely Benign

Met criteria codes 2
PM2_Supporting BS2
Not Met criteria codes 24
BP2 BP3 BP4 BP1 BP7 BP5 PS4 PS2 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PVS1 PM6 PM3 PM1 PM4 PM5 BS4 BS3 BS1

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.1493A>C (p.Asp498Ala) variant is present at <1/100,000 alleles in the European non-Finnish subpopulation of the gnomAD cohort (1/113,758 alleles; PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been seen in at least 10 individuals without DCG, SRC tumors, or LBC & whose families do not suggest HDGC (BS2; SCV000279435.9, SCV000637728.4). 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: PM2_Supporting, BS2.
Met criteria codes
PM2_Supporting
<1/100,000 alleles: Non-Finnish European AF is 0.00001 (0.001%, 1/113,758 alleles)
BS2
Variant seen in at least 10 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC (SCV000279435.9, SCV000637728.4). Four individuals with beast cancer either with a single diagnosis of LBC or pathology not known (SCV000279435.9, SCV000637728.4).
Not Met criteria codes
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
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
PS4
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
PS1
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
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 significant differences in prediction of splicing alterations (HSF, MES)
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
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
Approved on: 2023-08-18
Published on: 2023-08-18
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