Variant: NM_004360.4(CDH1):c.1849G>A (p.Ala617Thr)

CA121991

12232 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 8fe2e0a3-670f-4cdb-bbf8-3836f7fc45e9

Approved on: 2023-08-08

Published on: 2023-08-08

HGVS expressions

NM_004360.4:c.1849G>A
NM_004360.4(CDH1):c.1849G>A (p.Ala617Thr)
NC_000016.10:g.68822138G>A
CM000678.2:g.68822138G>A
NC_000016.9:g.68856041G>A
CM000678.1:g.68856041G>A
NC_000016.8:g.67413542G>A
NG_008021.1:g.89847G>A
ENST00000261769.10:c.1849G>A
ENST00000261769.9:c.1849G>A
ENST00000422392.6:c.1666G>A
ENST00000562836.5:n.1920G>A
ENST00000566510.5:c.*515G>A
ENST00000566612.5:c.*89G>A
ENST00000611625.4:c.1912G>A
ENST00000612417.4:c.1830+19G>A
ENST00000621016.4:c.1849G>A
NM_004360.3:c.1849G>A
NM_001317184.1:c.1666G>A
NM_001317185.1:c.301G>A
NM_001317186.1:c.-117G>A
NM_004360.5:c.1849G>A
NM_001317184.2:c.1666G>A
NM_001317185.2:c.301G>A
NM_001317186.2:c.-117G>A

Benign

• Met criteria codes: BA1

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

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Evidence submitted by expert panel

CDH1 VCEP

The c.1849G>A (p.Ala617Thr) variant has an allele frequency of 0.04479 (4.5%, 1,076/24,022 alleles) in the African subpopulation of the gnomAD cohort (BA1). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1.

Met criteria codes

• BA1: 1000 Genomes: 5.144% in AFR G: 0.94856 (1254) A: 0.05144 (68) ExAC: 4.622% in African (Allele count 481, 15 homozygotes) ESP6500: African American 4.709% (207)

Not Met criteria codes

• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: Does not meet Impact Threshold: REVEL, SIFT, PolyPhen2-HVAR, MutationTaster, MutationAssessor, FATHMM, PROVEAN, MetaSVM, MetaLR, CADD Splicing predictors (conflicting): HSF: "Alteration of an exonic ESE site. Potential alteration of splicing" MaxEntScan: GATgCAGAC (reference) MAXENT: -12.96 GATACAGAC (this Variant) MAXENT: -21.14 NNSPLICE: No new donor/acceptor site predicted due to c.1849G>A
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: 1000 Genomes: 5.144% in AFR G: 0.94856 (1254) A: 0.05144 (68) ExAC: 4.622% in African (Allele count 481, 15 homozygotes) ESP6500: African American 4.709% (207)
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: 1000 Genomes: 5.144% in AFR G: 0.94856 (1254) A: 0.05144 (68) ExAC: 4.622% in African (Allele count 481, 15 homozygotes) ESP6500: African American 4.709% (207)
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: Does not meet Impact Threshold: REVEL, SIFT, PolyPhen2-HVAR, MutationTaster, MutationAssessor, FATHMM, PROVEAN, MetaSVM, MetaLR, CADD Splicing predictors (conflicting): HSF: "Alteration of an exonic ESE site. Potential alteration of splicing" MaxEntScan: GATgCAGAC (reference) MAXENT: -12.96 GATACAGAC (this Variant) MAXENT: -21.14 NNSPLICE: No new donor/acceptor site predicted due to c.1849G>A
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline