NM_000038.6(APC):c.5009C>T (p.Ala1670Val) AND Familial adenomatous polyposis 1

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jan 28, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000122783.28

Allele description [Variation Report for NM_000038.6(APC):c.5009C>T (p.Ala1670Val)]

NM_000038.6(APC):c.5009C>T (p.Ala1670Val)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.5009C>T (p.Ala1670Val)

HGVS:

NC_000005.10:g.112840603C>T
NG_008481.4:g.153083C>T
NM_000038.6:c.5009C>TMANE SELECT
NM_001127510.3:c.5009C>T
NM_001127511.3:c.4955C>T
NM_001354895.2:c.5009C>T
NM_001354896.2:c.5063C>T
NM_001354897.2:c.5039C>T
NM_001354898.2:c.4934C>T
NM_001354899.2:c.4925C>T
NM_001354900.2:c.4886C>T
NM_001354901.2:c.4832C>T
NM_001354902.2:c.4736C>T
NM_001354903.2:c.4706C>T
NM_001354904.2:c.4631C>T
NM_001354905.2:c.4529C>T
NM_001354906.2:c.4160C>T
NP_000029.2:p.Ala1670Val
NP_001120982.1:p.Ala1670Val
NP_001120983.2:p.Ala1652Val
NP_001341824.1:p.Ala1670Val
NP_001341825.1:p.Ala1688Val
NP_001341826.1:p.Ala1680Val
NP_001341827.1:p.Ala1645Val
NP_001341828.1:p.Ala1642Val
NP_001341829.1:p.Ala1629Val
NP_001341830.1:p.Ala1611Val
NP_001341831.1:p.Ala1579Val
NP_001341832.1:p.Ala1569Val
NP_001341833.1:p.Ala1544Val
NP_001341834.1:p.Ala1510Val
NP_001341835.1:p.Ala1387Val
LRG_130t1:c.5009C>T
LRG_130:g.153083C>T
NC_000005.9:g.112176300C>T
NM_000038.4:c.5009C>T
NM_000038.5:c.5009C>T
p.A1670V

Protein change:

A1387V

Links:

dbSNP: rs202228932

NCBI 1000 Genomes Browser:

rs202228932

Molecular consequence:

NM_000038.6:c.5009C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.5009C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.4955C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.5009C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.5063C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.5039C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.4934C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.4925C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.4886C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.4832C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.4736C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.4706C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.4631C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.4529C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.4160C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000166040	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 28, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000784749	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Nov 21, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26207792, 27705013, 26580448 Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV000838125	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV004018748	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Feb 21, 2023)	unknown	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients.

Lincoln SE, Kobayashi Y, Anderson MJ, Yang S, Desmond AJ, Mills MA, Nilsen GB, Jacobs KB, Monzon FA, Kurian AW, Ford JM, Ellisen LW.

J Mol Diagn. 2015 Sep;17(5):533-44. doi: 10.1016/j.jmoldx.2015.04.009. Epub 2015 Jul 22.

PubMed [citation]

PMID:: 26207792

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000166040.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000784749.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV000838125.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004018748.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely benign. This variant has been observed in conjunction with multiple pathogenic variants, reducing the likelihood this variant itself is pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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