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NM_000038.6(APC):c.5009C>T (p.Ala1670Val) AND Carcinoma of colon

Germline classification:
Likely benign (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001353632.10

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:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000591183Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely benignunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591183.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The APC p.Ala1670Val variant was not identified in the literature nor was it identified in the Genesight-COGR, Cosmic, Zhejiang Colon Cancer Database, databases. The variant was identified in dbSNP (ID: rs202228932) “With Uncertain significance allele”, ClinVar (classified with conflicting interpretations of pathogenicity; submitters: likely benign by Ambry Genetics and uncertain significance by Invitae, GeneDx and Department of Pathology and Laboratory Medicine (Sinai Health System)), Clinvitae (3x), Insight Colon Cancer Gene Variant Database (1X), and in control databases in 48 of 275942 chromosomes at a frequency of 0.0002 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: European Non-Finnish in 41 of 125686 chromosomes (frequency: 0.0003) and European Finnish in 7 of 25768 chromosomes (frequency: 0.0003). The variant was also identified by our laboratory in 1 individual with tubular adenomas. The p.Ala1670 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of the Val variant impacting the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024