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_004360.5(CDH1):c.49-3C>T

CA167975

142294 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 385373d2-025f-43b5-be8a-5c0aa6af9901

HGVS expressions

NM_004360.5:c.49-3C>T

NM_004360.5(CDH1):c.49-3C>T

NC_000016.10:g.68738294C>T

CM000678.2:g.68738294C>T

NC_000016.9:g.68772197C>T

CM000678.1:g.68772197C>T

NC_000016.8:g.67329698C>T

NG_008021.1:g.6003C>T

ENST00000261769.10:c.49-3C>T

ENST00000261769.9:c.49-3C>T

ENST00000422392.6:c.49-3C>T

ENST00000566510.5:c.49-3C>T

ENST00000566612.5:c.49-3C>T

ENST00000611625.4:c.49-3C>T

ENST00000612417.4:c.49-3C>T

ENST00000621016.4:c.49-3C>T

NM_004360.3:c.49-3C>T

NM_001317184.1:c.49-3C>T

NM_001317185.1:c.-1567-3C>T

NM_001317186.1:c.-1771-3C>T

NM_004360.4:c.49-3C>T

NM_001317184.2:c.49-3C>T

NM_001317185.2:c.-1567-3C>T

NM_001317186.2:c.-1771-3C>T

Likely Benign

BS2 BP4

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

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.49-3C>T variant has been observed in at least 10 individuals without DGC, SRC tumours, or LBC & whose families do not suggest HDGC (BS2; SCV000186304.5, SCV000288486.4). There are at least 3 in silico predictors in agreement that this variant does not affect splicing (BP4). In summary, 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, BP4.

BS2

This variant was identified in 26 families who do not meet IGCLC criteria for HDGC (SCV000186304.5, SCV000288486.4).

BP4

This variant is not predicted to alter splicing by multiple splice site predictors.

BS4

To our knowledge, segregation of this variant has not been reported in an HDGC family.

BS3

To our knowledge, functional studies have not been reported for this variant.

BS1

This variant occurs at a frequency of 0.00002 (3 in 188,188) in gnomAD, with a maximum allele frequency of 0.00012 (2 in 17,020) in the African subpopulation.

BP5

To our knowledge, this variant has not been reported in a case with an alternate molecular basis for disease.

BP7

BP7 does not apply to intronic variants.

BP2

To our knowledge, this variant has not been reported in cis or trans with a pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP1

BP1 does not apply to CDH1.

PVS1

PVS1 does not apply to intronic variants.

PS2

To our knowledge, this variant has not been reported as de novo.

PS4

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

PS3

To our knowledge, functional studies have not been reported for this variant.

PS1

PS1 does not apply to this variant.

PP4

PP4 does not apply to CDH1.

PP1

To our knowledge, segregation of this variant has not been reported in an HDGC family.

PP3

This variant is not predicted to alter splicing by multiple splice site predictors.

PP2

PP2 does not apply to CDH1.

BA1

This variant occurs at a frequency of 0.00002 (3 in 188,188) in gnomAD, with a maximum allele frequency of 0.00012 (2 in 17,020) in the African subpopulation.

PM6

To our knowledge, this variant has not been reported as de novo.

PM2

This variant occurs at a frequency of 0.00002 (3 in 188,188) in gnomAD, with a maximum allele frequency of 0.00012 (2 in 17,020) in the African subpopulation. Therefore, this variant does not meet criteria for PM2.

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM5

PM5 does not apply to CDH1.

Approved on: 2023-08-17

Published on: 2023-08-17

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