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_004360.5(CDH1):c.1565C>T (p.Thr522Ile)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA337526

216588 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bfceaed6-bdd0-41f8-857a-4ee3c6a14e03

Approved on: 2023-08-03

Published on: 2023-08-03

HGVS expressions

NM_004360.5:c.1565C>T

NM_004360.5(CDH1):c.1565C>T (p.Thr522Ile)

NC_000016.10:g.68815759C>T

CM000678.2:g.68815759C>T

NC_000016.9:g.68849662C>T

CM000678.1:g.68849662C>T

NC_000016.8:g.67407163C>T

NG_008021.1:g.83468C>T

ENST00000261769.10:c.1565C>T

ENST00000261769.9:c.1565C>T

ENST00000422392.6:c.1382C>T

ENST00000562836.5:n.1636C>T

ENST00000566510.5:c.*231C>T

ENST00000566612.5:c.1565C>T

ENST00000611625.4:c.1628C>T

ENST00000612417.4:c.1565C>T

ENST00000621016.4:c.1565C>T

NM_004360.3:c.1565C>T

NM_001317184.1:c.1382C>T

NM_001317185.1:c.17C>T

NM_001317186.1:c.-255C>T

NM_004360.4:c.1565C>T

NM_001317184.2:c.1382C>T

NM_001317185.2:c.17C>T

NM_001317186.2:c.-255C>T

Benign

BP2_Strong BS2

BA1 PS4 PM2 BS1

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 NM_004360.5(CDH1): c.1565C>T (p.Thr522Ile) 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). This variant was observed in the homozygous state in 1 individual without personal and/or family history of DGC, LBC, or SRC tumors (BP2_strong; internal laboratory contributors). This variant is known in one family with HDGC criteria (ERN_GENTURIS). In summary, the clinical significance of this variant is classified as benign based on BS2 and BP2_strong. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel: BS2, BP2_strong. (CDH1 VCEP specifications version 3.1; 06/26/2023)

BP2_Strong

This variant is observed in the homozygous state in 1 individual without personal and/or family history of DGC, LBC, or SRC tumors (BP2; Ambry)

BS2

This variant has been observed in 80 heterozygous and 1 homozygous individuals with no diffuse gastric cancer, signet ring cell carcinoma or lobular breast cancer and/or whose family histories do not suggest HDGC (BS2; GeneDX, Ambry, Invitae). Note that this includes one individual with family history of unspecified gastric cancer.

BA1

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

PS4

This variant has been reported in 1 family meeting HDGC criteria (PS4_supportive); ERN_GENTURIS). PS4 is not applied since the percentage of families meeting HDGC criteria is bellow 30%.

PM2

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

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.