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]

Variant: NM_004360.4(CDH1):c.1162G>A (p.Glu388Lys)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA157986

127906 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5c24cb6c-a751-4e76-83ab-baccc23c4caa

Approved on: 2023-08-10

Published on: 2023-08-10

HGVS expressions

NM_004360.4:c.1162G>A

NM_004360.4(CDH1):c.1162G>A (p.Glu388Lys)

NC_000016.10:g.68813337G>A

CM000678.2:g.68813337G>A

NC_000016.9:g.68847240G>A

CM000678.1:g.68847240G>A

NC_000016.8:g.67404741G>A

NG_008021.1:g.81046G>A

ENST00000261769.10:c.1162G>A

ENST00000261769.9:c.1162G>A

ENST00000422392.6:c.1137+1074G>A

ENST00000562836.5:n.1233G>A

ENST00000565810.1:n.206G>A

ENST00000566510.5:c.1006G>A

ENST00000566612.5:c.1162G>A

ENST00000611625.4:c.1162G>A

ENST00000612417.4:c.1162G>A

ENST00000621016.4:c.1162G>A

NM_004360.3:c.1162G>A

NM_001317184.1:c.1137+1074G>A

NM_001317185.1:c.-454G>A

NM_001317186.1:c.-658G>A

NM_004360.5:c.1162G>A

NM_001317184.2:c.1137+1074G>A

NM_001317185.2:c.-454G>A

NM_001317186.2:c.-658G>A

NM_004360.5(CDH1):c.1162G>A (p.Glu388Lys)

Benign

BP2_Strong BS2

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

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.1162G>A (p.Glu388Lys) variant was observed in the homozygous state in an individual without a personal and/or family history of diffuse gastric cancer, lobular breast cancer (BP2_Strong; SCV000254804.3). The variant has also 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, 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): BP2_Strong, BS2.

BP2_Strong

Observed in homozygous state in individual w/o dx of HDGC

BS2

Observed in 34 individuals w/o a dx of HDGC

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

REVEL, SIFT, PolyPhen2, MutationAssessor, FATHMM, PROVEAN, MetaSVM, MetaLR, and CADD all predict no impact on gene product.

PM6

Insufficient data

PM2

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

PM3

N/A for HDGC

PM1

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

PM4

N/A

PM5

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

BS4

Insufficient data

BS3

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

BS1

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

BP3

N/A

BP1

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

BP4

REVEL, SIFT, PolyPhen2, MutationAssessor, FATHMM, PROVEAN, MetaSVM, MetaLR, and CADD all predict no impact on gene product.

BP5

Insufficient data

BP7

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

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.

BA1

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

PVS1

Not a null variant

Curation History

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