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NM_000038.6(APC):c.1825G>A (p.Val609Ile) 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:
RCV001353927.8

Allele description [Variation Report for NM_000038.6(APC):c.1825G>A (p.Val609Ile)]

NM_000038.6(APC):c.1825G>A (p.Val609Ile)

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.1825G>A (p.Val609Ile)
Other names:
p.V609I:GTA>ATA
HGVS:
  • NC_000005.10:g.112835032G>A
  • NG_008481.4:g.147512G>A
  • NM_000038.6:c.1825G>AMANE SELECT
  • NM_001127510.3:c.1825G>A
  • NM_001127511.3:c.1771G>A
  • NM_001354895.2:c.1825G>A
  • NM_001354896.2:c.1879G>A
  • NM_001354897.2:c.1855G>A
  • NM_001354898.2:c.1750G>A
  • NM_001354899.2:c.1741G>A
  • NM_001354900.2:c.1702G>A
  • NM_001354901.2:c.1648G>A
  • NM_001354902.2:c.1552G>A
  • NM_001354903.2:c.1522G>A
  • NM_001354904.2:c.1447G>A
  • NM_001354905.2:c.1345G>A
  • NM_001354906.2:c.976G>A
  • NP_000029.2:p.Val609Ile
  • NP_001120982.1:p.Val609Ile
  • NP_001120983.2:p.Val591Ile
  • NP_001341824.1:p.Val609Ile
  • NP_001341825.1:p.Val627Ile
  • NP_001341826.1:p.Val619Ile
  • NP_001341827.1:p.Val584Ile
  • NP_001341828.1:p.Val581Ile
  • NP_001341829.1:p.Val568Ile
  • NP_001341830.1:p.Val550Ile
  • NP_001341831.1:p.Val518Ile
  • NP_001341832.1:p.Val508Ile
  • NP_001341833.1:p.Val483Ile
  • NP_001341834.1:p.Val449Ile
  • NP_001341835.1:p.Val326Ile
  • LRG_130t1:c.1825G>A
  • LRG_130:g.147512G>A
  • NC_000005.9:g.112170729G>A
  • NM_000038.4:c.1825G>A
  • NM_000038.5:c.1825G>A
  • p.V609I
Protein change:
V326I
Links:
dbSNP: rs147863331
NCBI 1000 Genomes Browser:
rs147863331
Molecular consequence:
  • NM_000038.6:c.1825G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.1825G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.1771G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.1825G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.1879G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.1855G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.1750G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.1741G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.1702G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.1552G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.1522G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.1447G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.1345G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.976G>A - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000591092Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely benignunknownclinical testing

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), SCV000591092.2

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

Description

The APC p.Val609Ile variant was identified in 5 of 8718 proband chromosomes (frequency: 0.0006) from individuals or families with colorectal cancer (Kerr 2012, Pearlman 2017, Yurgelun 2015, Yurgelun 2017). The variant was also identified in dbSNP (ID: rs147863331) as "With other allele", ClinVar (classified as likely benign by Invitae, GeneDx, Ambry Genetics and three other submitters; as uncertain significance by Counsyl), and in LOVD 3.0 (1x as VUS). The variant was not identified in UMD-LSDB. The variant was identified in control databases in 83 of 277028 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the African population in 83 of 24034 chromosomes (freq: 0.003), while the variant was not observed in the Other, Latino, European, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The variant was identified in our laboratory with a co-occurring pathogenic APC variant (c.4391_4394del, p.Glu1464Valfs*8), increasing the likelihood that the p.Val609Ile variant does not have clinical significance. The p.Val609 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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: Oct 26, 2024