The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_004360.5(CDH1):c.32_34TGC[7] (p.Leu14_Leu15dup)

CA168401

142455 (ClinVar)

Gene: CDH1
Condition: hereditary diffuse gastric cancer
Inheritance Mode: Autosomal dominant inheritance
UUID: 32a09493-4519-46f6-b57a-e60d03a9272e
Approved on: 2020-04-21
Published on: 2020-06-03

HGVS expressions

NM_004360.5:c.32_34TGC[7]
NM_004360.5(CDH1):c.32_34TGC[7] (p.Leu14_Leu15dup)
NC_000016.10:g.68737456_68737461dup
CM000678.2:g.68737456_68737461dup
NC_000016.9:g.68771359_68771364dup
CM000678.1:g.68771359_68771364dup
NC_000016.8:g.67328860_67328865dup
NG_008021.1:g.5165_5170dup
ENST00000261769.10:c.41_46dup
ENST00000261769.9:c.41_46dup
ENST00000422392.6:c.41_46dup
ENST00000566510.5:c.41_46dup
ENST00000566612.5:c.41_46dup
ENST00000611625.4:c.41_46dup
ENST00000612417.4:c.41_46dup
ENST00000621016.4:c.41_46dup
NM_004360.3:c.41_46dup
NM_001317184.1:c.41_46dup
NM_001317185.1:c.-1575_-1570dup
NM_001317186.1:c.-1779_-1774dup
NM_004360.4:c.41_46dup
NM_004360.5:c.41_46dup
NM_001317184.2:c.41_46dup
NM_001317185.2:c.-1575_-1570dup
NM_001317186.2:c.-1779_-1774dup
More

Likely Benign

Met criteria codes 2
PM2 BS2
Not Met criteria codes 24
PVS1 PS1 PS2 PS3 PS4 BA1 PP1 PP2 PP3 PP4 PM6 PM1 PM3 PM5 PM4 BS1 BS4 BS3 BP5 BP7 BP4 BP3 BP1 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.32_34TGC[7] (p.Leu14_Leu15dup) variant results in an in-frame insertion in exon 1. This variant has a frequency of 0.0008% in gnomAD (1 of 124,448) (PM2; https://gnomad.broadinstitute.org/). However, this region has poor coverage and allele frequency estimates may not be reliable. This variant has also been identified in at least ten individuals without DGC, SRC tumours and LBC and whose families do not suggest HDGC (BS2, SCV000569203.4, SCV000186596.5, SCV000545430.4). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2, PM2.
Met criteria codes
PM2
This variant was identified in 1 of 124,448 alleles in gnomAD. Note that this variant is covered in fewer than 50% of individuals in gnomAD v2.1.1 exomes and allele frequency estimates may not be reliable.
BS2
This variant was identified in 21 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (SCV000569203.4, SCV000186596.5, SCV000545430.4). Note that 4 individuals reported gastric cancer (unknown histology) or lobular breast cancer in their family, but whose families are not otherwise suggestive of HDGC. Therefore, this variant meets criteria for BS2 based on at least 10 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC.
Not Met criteria codes
PVS1
PVS1 does not apply to this variant.
PS1
PS1 does not apply to this variant.
PS2
To our knowledge, this variant has not been reported as de novo.
PS3
PS3 does not apply to this variant.
PS4
This variant was identified in 21 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (SCV000569203.4, SCV000186596.5, SCV000545430.4). Note that 4 individuals reported gastric cancer (unknown histology) or lobular breast cancer in their family, but whose families are not otherwise suggestive of HDGC. Therefore, this variant meets criteria for BS2 based on at least 10 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC.
BA1
This variant was identified in 1 of 124,448 alleles in gnomAD. Note that this variant is covered in fewer than 50% of individuals in gnomAD v2.1.1 exomes and allele frequency estimates may not be reliable.
PP1
To our knowledge, segregation of this variant has not been reported.
PP2
PP2 does not apply to CDH1.
PP3
PP3 does not apply to this variant.
PP4
PP4 does not apply to CDH1.
PM6
To our knowledge, this variant has not been reported as de novo.
PM1
PM1 does not apply to CDH1.
PM3
PM3 does not apply to CDH1.
PM5
PM5 does not apply to CDH1.
PM4
This variant results in the insertion of two leucine molecules in a short repeat region encoding a string of five leucines in the signal peptide region (exon 1). Therefore, the effect of this variant on protein function is uncertain.
BS1
This variant was identified in 1 of 124,448 alleles in gnomAD. Note that this variant is covered in fewer than 50% of individuals in gnomAD v2.1.1 exomes and allele frequency estimates may not be reliable.
BS4
To our knowledge, segregation of this variant has not been reported.
BS3
BS3 does not apply to this variant.
BP5
To our knowledge, this variant has not been identified in a case with an alternate molecular basis for disease.
BP7
BP7 does not apply to this variant.
BP4
BP4 does not apply to this variant.
BP3
BP3 does not apply to CDH1.
BP1
BP1 does not apply to CDH1.
BP2
To our knowledge, this variant has not been reported in cis or trans with a known pathogenic variant.
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.
¤ Powered by BCM's Genboree.