Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_004360.5(CDH1):c.113C>A (p.Thr38Lys)

CA8129795

231383 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f0755992-c309-4d96-b135-ffb7f9983bf0

HGVS expressions

NM_004360.5:c.113C>A
NM_004360.5(CDH1):c.113C>A (p.Thr38Lys)
NC_000016.10:g.68738361C>A
CM000678.2:g.68738361C>A
NC_000016.9:g.68772264C>A
CM000678.1:g.68772264C>A
NC_000016.8:g.67329765C>A
NG_008021.1:g.6070C>A
ENST00000261769.10:c.113C>A
ENST00000261769.9:c.113C>A
ENST00000422392.6:c.113C>A
ENST00000566510.5:c.113C>A
ENST00000566612.5:c.113C>A
ENST00000611625.4:c.113C>A
ENST00000612417.4:c.113C>A
ENST00000621016.4:c.113C>A
NM_004360.3:c.113C>A
NM_001317184.1:c.113C>A
NM_001317185.1:c.-1503C>A
NM_001317186.1:c.-1707C>A
NM_004360.4:c.113C>A
NM_001317184.2:c.113C>A
NM_001317185.2:c.-1503C>A
NM_001317186.2:c.-1707C>A

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 25
PS2 PS4 PS3 PS1 BP5 BP7 BP2 BP3 BP4 BP1 PP4 PP1 PP3 PP2 BA1 PVS1 PM6 PM2 PM3 PM1 PM4 PM5 BS4 BS3 BS1

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.113C>A (p.Thr38Lys) variant results in a non-synonymous amino acid substitution in exon 2 of CDH1. This variant has been observed in at least 10 individuals without DGC, LBC or SRC tumors and whose families do not suggest HDGC (BS2; SCV000637699.3, SCV000275215.5). In summary, this variant meets criteria to be classified as likely benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2.
Met criteria codes
BS2
This variant was identified in ten individuals without DGC, LBC or SRC tumours and whose families do not suggest HDGC (SCV000637699.3, SCV000275215.5).
Not Met criteria codes
PS2
To our knowledge, this variant has not been reported de novo in an individual with HDGC.
PS4
This variant was identified in ten individuals without DGC, LBC or SRC tumours and whose families do not suggest HDGC.
PS3
No functional studies demonstrating an impact on splicing have been reported for this variant.
PS1
No pathogenic variants resulting in the same amino acid change at this position have been established.
BP5
This variant has not been reported in an individual with an alternate molecular basis for disease.
BP7
BP7 does not apply to this variant.
BP2
To our knowledge, this variant has not been reported in cis or trans with a known pathogenic variant.
BP3
BP3 does not apply to CDH1.
BP4
This variant is not predicted to impact splicing by multiple computational predictors.
BP1
BP1 does not apply to CDH1.
PP4
PP4 does not apply to CDH1.
PP1
Segregation not known.
PP3
This variant is not predicted to impact splicing by multiple computational predictors.
PP2
PP2 does not apply to CDH1.
BA1
This allele is present at a frequency of 0.00002 (3 in 156,704 alleles) in gnomAD v2, with a maximum frequency of 0.00009 (2 in 22,744 alleles) in the South Asian subpopulation. Note that this allele occurs at a frequency of 0.000006977 (1 in 143,328 alleles) in gnomAD v3, with a maximum frequency of 0.00007320 (1 in 13,662 alleles) in the Latino subpopulation.
PVS1
PVS1 does not apply to this variant.
PM6
To our knowledge, this variant has not been reported de novo in an individual with HDGC.
PM2
This allele is present at a frequency of 0.00002 (3 in 156,704 alleles) in gnomAD v2, with a maximum frequency of 0.00009 (2 in 22,744 alleles) in the South Asian subpopulation. Note that this allele occurs at a frequency of 0.000006977 (1 in 143,328 alleles) in gnomAD v3, with a maximum frequency of 0.00007320 (1 in 13,662 alleles) in the Latino subpopulation.
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.
BS4
Segregation not known.
BS3
No functional studies demonstrating an impact on splicing have been reported for this variant.
BS1
This allele is present at a frequency of 0.00002 (3 in 156,704 alleles) in gnomAD v2, with a maximum frequency of 0.00009 (2 in 22,744 alleles) in the South Asian subpopulation. Note that this allele occurs at a frequency of 0.000006977 (1 in 143,328 alleles) in gnomAD v3, with a maximum frequency of 0.00007320 (1 in 13,662 alleles) in the Latino subpopulation.
Approved on: 2023-08-17
Published on: 2023-08-17
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