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.671G>A (p.Arg224His)

CA165387

41786 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 55957b0c-748d-4efe-8c6d-60dee2cb6bac
Approved on: 2023-08-09
Published on: 2023-08-10

HGVS expressions

NM_004360.5:c.671G>A
NM_004360.5(CDH1):c.671G>A (p.Arg224His)
NC_000016.10:g.68808832G>A
CM000678.2:g.68808832G>A
NC_000016.9:g.68842735G>A
CM000678.1:g.68842735G>A
NC_000016.8:g.67400236G>A
NG_008021.1:g.76541G>A
ENST00000261769.10:c.671G>A
ENST00000261769.9:c.671G>A
ENST00000422392.6:c.671G>A
ENST00000561751.1:n.438G>A
ENST00000562836.5:n.742G>A
ENST00000564676.5:n.953G>A
ENST00000566510.5:c.531+265G>A
ENST00000566612.5:c.671G>A
ENST00000567320.1:n.181G>A
ENST00000611625.4:c.671G>A
ENST00000612417.4:c.671G>A
ENST00000621016.4:c.671G>A
NM_004360.3:c.671G>A
NM_001317184.1:c.671G>A
NM_001317185.1:c.-945G>A
NM_001317186.1:c.-1149G>A
NM_004360.4:c.671G>A
NM_001317184.2:c.671G>A
NM_001317185.2:c.-945G>A
NM_001317186.2:c.-1149G>A
More

Benign

Met criteria codes 2
BP2_Strong BS2
Not Met criteria codes 24
PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM2 PM3 PM1 PM4 PM5 PVS1 BA1 BS4 BS3 BS1 BP5 BP7 BP3 BP4 BP1

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.671G>A (p.Arg224His) missense variant has a frequency of 0. 0.00003189 (8 of 250,850) in the gnomAD v2.1.1 cohort, with a maximum non-founder allele frequency of 0.00006179 (7 of 113,278) in the African subpopulation (http://gnomad.broadinstitute.org). This variant has been observed in >50 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC (BS2; SCV000637843.5, SCV000278911.9). This variant was observed in the homozygous state in an individual without DGC, SRC tumors or LBC and whose family does not suggest HDGC (BP2_Strong, internal laboratory contributor). In summary, the clinical significance of this variant is classified as benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP2_Strong.
Met criteria codes
BP2_Strong
homozygous in 1 proband
BS2
This variant has been observed in >50 individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC (BS2; SCV000637843.5, SCV000278911.9).
Not Met criteria codes
PS2
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
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
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
gnomAD frequency 0.00003189 (8 of 250,850 alleles)
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
gnomAD frequency 0.00003189 (8 of 250,850 alleles)
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
gnomAD frequency 0.00003189 (8 of 250,850 alleles)
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
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
Curation History
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