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]

Variant: NM_004360.4(CDH1):c.2451G>A (p.Ala817=)

CA186706

183842 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 20f73f9f-5a02-4ed6-855f-69e4e63e0e22
Approved on: 2023-08-17
Published on: 2023-08-17

HGVS expressions

NM_004360.4:c.2451G>A
NM_004360.4(CDH1):c.2451G>A (p.Ala817=)
NC_000016.10:g.68833301G>A
CM000678.2:g.68833301G>A
NC_000016.9:g.68867204G>A
CM000678.1:g.68867204G>A
NC_000016.8:g.67424705G>A
NG_008021.1:g.101010G>A
ENST00000261769.10:c.2451G>A
ENST00000261769.9:c.2451G>A
ENST00000422392.6:c.2268G>A
ENST00000562118.1:n.669G>A
ENST00000562836.5:n.2522G>A
ENST00000566510.5:c.*1117G>A
ENST00000566612.5:c.*691G>A
ENST00000611625.4:c.2514G>A
ENST00000612417.4:c.1854-890G>A
ENST00000621016.4:c.1866-902G>A
NM_004360.3:c.2451G>A
NM_001317184.1:c.2268G>A
NM_001317185.1:c.903G>A
NM_001317186.1:c.486G>A
NM_004360.5:c.2451G>A
NM_001317184.2:c.2268G>A
NM_001317185.2:c.903G>A
NM_001317186.2:c.486G>A
NM_004360.5(CDH1):c.2451G>A (p.Ala817=)
More

Likely Benign

Met criteria codes 2
BS2 BP7
Not Met criteria codes 24
BS4 BS3 BS1 BP5 BP2 BP3 BP4 BP1 PS2 PS3 PS4 PS1 BA1 PVS1 PP1 PP4 PP3 PP2 PM1 PM3 PM4 PM5 PM6 PM2

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.2451G>A variant is predicted silent and has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). The nucleotide is not conserved (BP7). Therefore, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP7.
Met criteria codes
BS2
>50 probands (and families) that do not meet clinical criteria for HDGC (SCV000253421.4). 45 families that do not meet clinical criteria for HDGC (SCV000213120.4). 22 propands that do not meet clinical criteria for HDGC (SCV000512531.4).
BP7
The nucleotide is not conserved. There are four primates (Rhesus, macaque, baboon, bushbaby) with the variant as the reference nucleotide.
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
Allele frequency is <0.1%. The gnomAD PopMax AF for East Asians is 0.007%. In total there are 17/282,864 total alleles in gnomAD v2.1.1, 0 homozygotes.
BP5
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
BP4
MaxEntScan and NNSplice predict no splice impact. HSF predicts activation of an exonic cryptic acceptor site.
BP1
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
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
PP1
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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