Variant: NM_000038.6(APC):c.220+1G>A

CA360617465

433598 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

UUID: b4c3c9f6-68c8-4734-96de-778a1063f875

Approved on: 2025-05-16

Published on: 2025-05-16

HGVS expressions

NM_000038.6:c.220+1G>A
NM_000038.6(APC):c.220+1G>A
NC_000005.10:g.112766411G>A
CM000667.2:g.112766411G>A
NC_000005.9:g.112102108G>A
CM000667.1:g.112102108G>A
NC_000005.8:g.112130007G>A
NG_008481.4:g.78891G>A
ENST00000502371.3:c.220+1G>A
ENST00000504915.3:c.220+1G>A
ENST00000505084.2:n.276+1G>A
ENST00000505350.2:c.*226+1G>A
ENST00000507379.6:c.250+1G>A
ENST00000509732.6:c.220+1G>A
ENST00000512211.7:c.220+1G>A
ENST00000257430.9:c.220+1G>A
ENST00000257430.8:c.220+1G>A
ENST00000507379.5:c.250+1G>A
ENST00000508376.6:c.220+1G>A
ENST00000508624.5:c.220+1G>A
ENST00000509732.5:c.220+1G>A
ENST00000512211.6:c.220+1G>A
NM_000038.5:c.220+1G>A
NM_001127510.2:c.220+1G>A
NM_001127511.2:c.250+1G>A
NM_001354895.1:c.220+1G>A
NM_001354896.1:c.220+1G>A
NM_001354897.1:c.250+1G>A
NM_001354898.1:c.145+1G>A
NM_001354899.1:c.220+1G>A
NM_001354900.1:c.43+1G>A
NM_001354901.1:c.43+1G>A
NM_001354902.1:c.250+1G>A
NM_001354903.1:c.220+1G>A
NM_001354904.1:c.145+1G>A
NM_001354905.1:c.43+1G>A
NM_001354906.1:c.-816+1G>A
NM_001127510.3:c.220+1G>A
NM_001127511.3:c.250+1G>A
NM_001354895.2:c.220+1G>A
NM_001354896.2:c.220+1G>A
NM_001354897.2:c.250+1G>A
NM_001354898.2:c.145+1G>A
NM_001354899.2:c.220+1G>A
NM_001354900.2:c.43+1G>A
NM_001354901.2:c.43+1G>A
NM_001354902.2:c.250+1G>A
NM_001354903.2:c.220+1G>A
NM_001354904.2:c.145+1G>A
NM_001354905.2:c.43+1G>A
NM_001354906.2:c.-816+1G>A

Pathogenic

• Met criteria codes: PM2_Supporting PS4_Supporting PVS1

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The NM_000038.6(APC):c.220+1G>A variant in APC occurs within the canonical splice donor site (+1) of intron 3. It is predicted to cause skipping of exon 3, resulting in a frameshift in a gene in which loss-of-function is an established disease mechanism (PVS1). This prediction is confirmed by RNA analysis (internal data from Ambry Genetics and Invitae). This variant has been reported in one family meeting phenotypic criteria, resulting in a total phenotype score of 1 (PS4_Supporting, [internal data from Ambry Genetics]). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: criteria PVS1, PS4_Supporting and PM2_Supporting applied (VCEP specifications v2.1.0; date of approval 11/24/2023).

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PS4_Supporting: This variant has been reported in one family meeting phenotypic criteria, resulting in a total phenotype score of 1 (PS4_Supporting, [internal data from Ambry Genetics]).
• PVS1: The NM_000038.6(APC):c.220+1G>A variant in APC occurs within the canonical splice donor site (+1) of intron 3. It is predicted to cause skipping of exon 3, resulting in a frameshift in a gene in which loss-of-function is an established disease mechanism (PVS1). This prediction is confirmed by RNA analysis (internal data from Ambry Genetics and Invitae).