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.48+5C>T

CA8129781

491543 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8b836460-28fb-4877-8402-7b4e8c19a81e

HGVS expressions

NM_004360.4:c.48+5C>T

NM_004360.4(CDH1):c.48+5C>T

NC_000016.10:g.68737468C>T

CM000678.2:g.68737468C>T

NC_000016.9:g.68771371C>T

CM000678.1:g.68771371C>T

NC_000016.8:g.67328872C>T

NG_008021.1:g.5177C>T

ENST00000261769.10:c.48+5C>T

ENST00000261769.9:c.48+5C>T

ENST00000422392.6:c.48+5C>T

ENST00000566510.5:c.48+5C>T

ENST00000566612.5:c.48+5C>T

ENST00000611625.4:c.48+5C>T

ENST00000612417.4:c.48+5C>T

ENST00000621016.4:c.48+5C>T

NM_004360.3:c.48+5C>T

NM_001317184.1:c.48+5C>T

NM_001317185.1:c.-1568+5C>T

NM_001317186.1:c.-1772+5C>T

NM_004360.5:c.48+5C>T

NM_001317184.2:c.48+5C>T

NM_001317185.2:c.-1568+5C>T

NM_001317186.2:c.-1772+5C>T

NM_004360.5(CDH1):c.48+5C>T

Likely Benign

BS2_Supporting BP4

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

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.48+5C>T variant was observed in at least 3 families without a personal and/or family history of diffuse gastric cancer, lobular breast cancer or a signet ring cell tumor (BP2_Supporting; internal data). There are at least 3 in silico predictors in agreement that this variant does not affect splicing (BP4). Therefore, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2_Supporting, BP4.

BS2_Supporting

Variant seen in >3 individuals from internal laboratory w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC.

BP4

Multiple tools predict no impact on splicing.

PVS1

Not applicable.

BA1

0.009% MAF

PS2

Not reported in the literature

PS1

Not applicable

PS4

Not reported in the literature

PS3

No functional studies available

PP3

Multiple tools predict no impact on splicing.

PP2

Not applicable

PP4

Not applicable

PP1

Not reported in the literature

PM6

Not reported in the literature

PM2

0.009% MAF

PM5

Not applicable

PM4

Not applicable

PM3

Not applicable

PM1

Not applicable

BS4

Not reported in the literature

BS3

No functional studies available

BS1

0.009% MAF

BP5

Variant not reported in the literature

BP7

Not applicable for intronic variants.

BP3

Not applicable

BP1

Not applicable

BP2

Variant not reported in the literature

Approved on: 2023-08-18

Published on: 2023-08-18

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