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_004360.5(CDH1):c.724G>A (p.Val242Ile)

CA166473

141805 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 23f45364-22dd-4a0c-acf0-4d8bea0c95ce
Approved on: 2023-08-10
Published on: 2023-08-10

HGVS expressions

NM_004360.5:c.724G>A
NM_004360.5(CDH1):c.724G>A (p.Val242Ile)
NC_000016.10:g.68810233G>A
CM000678.2:g.68810233G>A
NC_000016.9:g.68844136G>A
CM000678.1:g.68844136G>A
NC_000016.8:g.67401637G>A
NG_008021.1:g.77942G>A
ENST00000261769.10:c.724G>A
ENST00000261769.9:c.724G>A
ENST00000422392.6:c.724G>A
ENST00000561751.1:n.454+1385G>A
ENST00000562836.5:n.795G>A
ENST00000566510.5:c.568G>A
ENST00000566612.5:c.724G>A
ENST00000611625.4:c.724G>A
ENST00000612417.4:c.724G>A
ENST00000621016.4:c.724G>A
NM_004360.3:c.724G>A
NM_001317184.1:c.724G>A
NM_001317185.1:c.-892G>A
NM_001317186.1:c.-1096G>A
NM_004360.4:c.724G>A
NM_001317184.2:c.724G>A
NM_001317185.2:c.-892G>A
NM_001317186.2:c.-1096G>A
More

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
BS4 BS3 BS1 BP7 BP5 BP3 BP2 BP4 BP1 PS2 PS4 PS1 PS3 BA1 PVS1 PP1 PP4 PP3 PP2 PM5 PM4 PM1 PM3 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.724G>A (p.Val242Ile) missense variant has a frequency of 0.01002% in South Asians (2 of 19954 alleles) in the gnomAD v2.1.1 cohort. This variant has been observed in ≥10 (22) individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000185325.6, SCV000259887.6). In summary, the clinical significance of this variant is classified as of 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
Observed in 22 individuals without HDGC phenotypes (SCV000185325.6, SCV000259887.6).
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 published functional studies.
BS1
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
VarSEAK: No splicing effect. SpliceAI: Acceptor Loss: score = 0.07 at 1 bp. Donor Gain: score = 0.03 at 29 bp.
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
PS4
PMID: 28338653 - DCIS (does not meet criteria).
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No published functional studies.
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
VarSEAK: No splicing effect. SpliceAI: Acceptor Loss: score = 0.07 at 1 bp. Donor Gain: score = 0.03 at 29 bp.
PP2
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
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
PM2
gnomAD 2.1.1: 2 of 19954 alleles in South Asians (0.01002%). gnomAD 3.1: 1 of 5196 alleles in South Asians (0.01925%), >0.002%.
Curation History
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