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_000038.6(APC):c.705A>G (p.Leu235=)

CA012805

92349 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f6cb4954-a857-4ac2-a4db-5367f1a4f0d3
Approved on: 2023-02-18
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.705A>G
NM_000038.6(APC):c.705A>G (p.Leu235=)
NC_000005.10:g.112792505A>G
CM000667.2:g.112792505A>G
NC_000005.9:g.112128202A>G
CM000667.1:g.112128202A>G
NC_000005.8:g.112156101A>G
NG_008481.4:g.104985A>G
ENST00000257430.9:c.705A>G
ENST00000257430.8:c.705A>G
ENST00000507379.5:c.676-8774A>G
ENST00000508376.6:c.705A>G
ENST00000508624.5:c.705A>G
ENST00000512211.6:c.705A>G
NM_000038.5:c.705A>G
NM_001127510.2:c.705A>G
NM_001127511.2:c.676-8774A>G
NM_001354895.1:c.705A>G
NM_001354896.1:c.705A>G
NM_001354897.1:c.735A>G
NM_001354898.1:c.630A>G
NM_001354899.1:c.646-8774A>G
NM_001354900.1:c.528A>G
NM_001354901.1:c.528A>G
NM_001354902.1:c.735A>G
NM_001354903.1:c.705A>G
NM_001354904.1:c.630A>G
NM_001354905.1:c.528A>G
NM_001354906.1:c.-331A>G
NM_001127510.3:c.705A>G
NM_001127511.3:c.676-8774A>G
NM_001354895.2:c.705A>G
NM_001354896.2:c.705A>G
NM_001354897.2:c.735A>G
NM_001354898.2:c.630A>G
NM_001354899.2:c.646-8774A>G
NM_001354900.2:c.528A>G
NM_001354901.2:c.528A>G
NM_001354902.2:c.735A>G
NM_001354903.2:c.705A>G
NM_001354904.2:c.630A>G
NM_001354905.2:c.528A>G
NM_001354906.2:c.-331A>G
More

Benign

Met criteria codes 4
BA1 BS2 BP4 BP7
Not Met criteria codes 12
PS2 PS4 PS3 PP4 PP1 PM6 PM1 PM3 BS4 BS3 BP2 BP5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.705A>G (p.Leu235=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing by multiple splicing predictors including SpliceAI, VarSEAK and MaxEntScan (BP4, BP7). This variant has been observed 3 (≥ 2) times in homozygous state in gnomAD 2.1.1 (BS2). The highest population minor allele frequency in the non-cancer population of gnomAD v2.1.1 is 0.004669 in the Finnish population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold (>0.001) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BS2, BP4, and BP7 (Specification Version 1.0; date of approval: 12/12/2022).
Met criteria codes
BA1
The highest population minor allele frequency in the non-cancer population of gnomAD v2.1.1 is 0.004669 in the Finnish population, which is higher than the ClinGen APC VCEP threshold (>0.001) for BA1, and therefore meets this criterion (BA1).
BS2
This variant has been observed 3 (≥ 2) times in homozygous state in gnomAD 2.1.1 (BS2).
BP4
The c.705A>G (p.Leu235=) variant is a synonymous (silent) variant that is not predicted by SpliceAI, varSEAK or MaxEntScan to impact splicing (BP4, BP7).
BP7
The c.705A>G (p.Leu235=) variant is a synonymous (silent) variant that is not predicted by SpliceAI and MaxEntScan to impact splicing (scores=0).
Not Met criteria codes
PS2
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
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
PM6
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
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
BP2
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
Curation History
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