Evidence Repository - Clinical Genome Resources

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_004360.4(CDH1):c.2413G>A (p.Asp805Asn)

CA157966

127925 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8f3f955a-56d1-4528-83ec-f23b19eb3126

HGVS expressions

NM_004360.4:c.2413G>A

NM_004360.4(CDH1):c.2413G>A (p.Asp805Asn)

NC_000016.10:g.68829771G>A

CM000678.2:g.68829771G>A

NC_000016.9:g.68863674G>A

CM000678.1:g.68863674G>A

NC_000016.8:g.67421175G>A

NG_008021.1:g.97480G>A

ENST00000261769.10:c.2413G>A

ENST00000261769.9:c.2413G>A

ENST00000422392.6:c.2230G>A

ENST00000562118.1:n.631G>A

ENST00000562836.5:n.2484G>A

ENST00000566510.5:c.*1079G>A

ENST00000566612.5:c.*653G>A

ENST00000611625.4:c.2476G>A

ENST00000612417.4:c.1853+3217G>A

ENST00000621016.4:c.1866-4432G>A

NM_004360.3:c.2413G>A

NM_001317184.1:c.2230G>A

NM_001317185.1:c.865G>A

NM_001317186.1:c.448G>A

NM_004360.5:c.2413G>A

NM_001317184.2:c.2230G>A

NM_001317185.2:c.865G>A

NM_001317186.2:c.448G>A

NM_004360.5(CDH1):c.2413G>A (p.Asp805Asn)

Benign

BA1

PVS1 BS2 BS4 BS3 BS1 BP3 BP2 BP1 BP4 BP7 BP5 PS2 PS4 PS1 PS3 PP1 PP4 PP2 PP3 PM1 PM4 PM3 PM5 PM6 PM2

Evidence Links 4

Expert Panel

CDH1 VCEP

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.2413G>A (p.Asp805Asn) variant has an allele frequency of 0.00207 (0.21%, 21/10,148 alleles) in the Ashkenazi Jewish subpopulation of the gnomAD cohort (BA1). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1.

BA1

Gnomad: 0.2% (21 AJ alleles)

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

Variant reported in at least one healthy individual undergoing exome sequencing and at least one person undergoing testing for Lynch syndrome.

Variant reported in at least one healthy individual undergoing exome sequencing. PubMed:24728327

Reported in at least one individual undergoing testing for Lynch syndrome. PubMed:25980754

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

In vitro experiment showed that CHO cells transfected with this variant displayed smaller cellular aggregates than wildtype.

This variant was seen in one individual with an orofacial cleft. In vitro experiment showed that CHO cells transfected with this variant displayed smaller cellular aggregates than wildtype. PubMed:23197654

BS1

Gnomad: 0.2% (21 AJ alleles)

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

BP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP4

REVEL: 0.374 Align GVGD: Class C0

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

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

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

In vitro experiment showed that CHO cells transfected with this variant displayed smaller cellular aggregates than wildtype.

PP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

Variant seen in one unaffected proband whose mother had LBC at 45, maternal aunt had DGC at 55 and maternal uncle had GC at 69 but it is unknown whether they carried the variant. It was also seen in one Jewish proband with HDGC.

This variant was seen in one Jewish individual with HDGC. PubMed:26182300

PP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

REVEL: 0.374 Align GVGD: Class C0

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

PM3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

Asp805Gly is VUS in clinvar.

PM6

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

Gnomad: 0.2% (21 AJ alleles)

Approved on: 2023-08-08

Published on: 2023-08-08

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