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]

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Variant: NM_004360.4(CDH1):c.2635G>A (p.Gly879Ser)

CA288064

127928 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 86a85614-4966-4b5e-9e92-5bcb810ab482

Approved on: 2023-08-17

Published on: 2023-08-17

HGVS expressions

NM_004360.4:c.2635G>A

NM_004360.4(CDH1):c.2635G>A (p.Gly879Ser)

NC_000016.10:g.68833485G>A

CM000678.2:g.68833485G>A

NC_000016.9:g.68867388G>A

CM000678.1:g.68867388G>A

NC_000016.8:g.67424889G>A

NG_008021.1:g.101194G>A

ENST00000261769.10:c.2635G>A

ENST00000261769.9:c.2635G>A

ENST00000422392.6:c.2452G>A

ENST00000562118.1:n.853G>A

ENST00000562836.5:n.2706G>A

ENST00000566510.5:c.*1301G>A

ENST00000566612.5:c.*875G>A

ENST00000611625.4:c.2698G>A

ENST00000612417.4:c.1854-706G>A

ENST00000621016.4:c.1866-718G>A

NM_004360.3:c.2635G>A

NM_001317184.1:c.2452G>A

NM_001317185.1:c.1087G>A

NM_001317186.1:c.670G>A

NM_004360.5:c.2635G>A

NM_001317184.2:c.2452G>A

NM_001317185.2:c.1087G>A

NM_001317186.2:c.670G>A

NM_004360.5(CDH1):c.2635G>A (p.Gly879Ser)

Likely Benign

BS2

PVS1 BA1 BS4 BS3 BS1 BP7 BP5 BP3 BP2 BP1 BP4 PS2 PS4 PS3 PS1 PP4 PP1 PP2 PP3 PM4 PM3 PM1 PM5 PM6 PM2

Evidence Links 0

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.2635G>A (p.Gly879Ser) variant 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). In summary, the clinical significance of this variant is classified as likely benign based on BS2 alone. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2.

BS2

Observed in 289 individuals w/o dx of HDGC.

PVS1

Not a null variant

BA1

ExAC = 0.00017 (total); 1000 Genomes = 0.00023 (ESP6500: African American), 0.00012 (ESP6500: European American)

BS4

Insufficient data

BS3

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

BS1

ExAC = 0.00017 (total); 1000 Genomes = 0.00023 (ESP6500: African American), 0.00012 (ESP6500: European American)

BP7

HSF: "Alteration of an exonic ESE site. Potential alteration of splicing."

BP5

Insufficient data

BP3

N/A

BP2

Insufficient data

BP1

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

BP4

Conflicting computational evidence. REVEL, SIFT, FATHMM, MetaSVM, MetaLR, CADD suggest no impact on gene product. PolyPHEN2-HVAR, MutationTaster, MutationAssessor, PROVEAN suggest deleterious effect on gene product.

PS2

Insufficient data

PS4

Insufficient data

PS3

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

PS1

The current variant is the only variant found in this codon in ClinVar.

PP4

Insufficient data

PP1

Insufficient data

PP2

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

PP3

PM4

N/A

PM3

N/A for HDGC

PM1

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

PM5

The current variant is the only variant found in this codon in ClinVar.

PM6

Insufficient data

PM2

ExAC = 0.00017 (total); 1000 Genomes = 0.00023 (ESP6500: African American), 0.00012 (ESP6500: European American)

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