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NM_000038.6(APC):c.1956C>T (p.His652=) AND Carcinoma of colon

Germline classification:
Pathogenic (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:
RCV000502897.10

Allele description [Variation Report for NM_000038.6(APC):c.1956C>T (p.His652=)]

NM_000038.6(APC):c.1956C>T (p.His652=)

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.1956C>T (p.His652=)
Other names:
NM_000038.6(APC):c.1956C>T; p.His652=
HGVS:
  • NC_000005.10:g.112835163C>T
  • NG_008481.4:g.147643C>T
  • NM_000038.6:c.1956C>TMANE SELECT
  • NM_001127510.3:c.1956C>T
  • NM_001127511.3:c.1902C>T
  • NM_001354895.2:c.1956C>T
  • NM_001354896.2:c.2010C>T
  • NM_001354897.2:c.1986C>T
  • NM_001354898.2:c.1881C>T
  • NM_001354899.2:c.1872C>T
  • NM_001354900.2:c.1833C>T
  • NM_001354901.2:c.1779C>T
  • NM_001354902.2:c.1683C>T
  • NM_001354903.2:c.1653C>T
  • NM_001354904.2:c.1578C>T
  • NM_001354905.2:c.1476C>T
  • NM_001354906.2:c.1107C>T
  • NP_000029.2:p.His652=
  • NP_001120982.1:p.His652=
  • NP_001120983.2:p.His634=
  • NP_001341824.1:p.His652=
  • NP_001341825.1:p.His670=
  • NP_001341826.1:p.His662=
  • NP_001341827.1:p.His627=
  • NP_001341828.1:p.His624=
  • NP_001341829.1:p.His611=
  • NP_001341830.1:p.His593=
  • NP_001341831.1:p.His561=
  • NP_001341832.1:p.His551=
  • NP_001341833.1:p.His526=
  • NP_001341834.1:p.His492=
  • NP_001341835.1:p.His369=
  • LRG_130:g.147643C>T
  • NC_000005.9:g.112170860C>T
  • NM_000038.5:c.1956C>T
Links:
dbSNP: rs1064793716
NCBI 1000 Genomes Browser:
rs1064793716
Molecular consequence:
  • NM_000038.6:c.1956C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001127510.3:c.1956C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001127511.3:c.1902C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354895.2:c.1956C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354896.2:c.2010C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354897.2:c.1986C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354898.2:c.1881C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354899.2:c.1872C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354900.2:c.1833C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354901.2:c.1779C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354902.2:c.1683C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354903.2:c.1653C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354904.2:c.1578C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354905.2:c.1476C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354906.2:c.1107C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
1

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
SCV000591098Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Pathogenicunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not 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), SCV000591098.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The APC p.His652His variant was identified in 2 of 2512 proband chromosomes (frequency: 0.001) from German and Czech individuals or families with FAP/AFAP (Friedl 2005, Schwarzova 2013). Aretz et al (2004) were first to show this silent variant resulted in exon 14 skipping similar to substitutions at highly conserved splice acceptor and donor sites, versus the alternative splicing nature of exon 14 seen in normal controls, which was contrary to calls made by splice prediction models. This finding was also seen by Schwarzova (2013), in a patient with AFAP, who by RNA based RT-PCR analysis was shown to have the same or higher amounts of the mutant transcript in his blood, healthy colon and polyp tissue, compared to the blood and colon mucosa of healthy individuals. The variant was not identified in dbSNP, 1000 Genomes Project, NHLBI GO Exome Sequencing Project , the Exome Aggregation Consortium database, Clinvitae database, Zhejiang Colon Cancer Database (LOVD), ClinVar database, GeneInsight - COGR database, and UMD; but was identified in COSMIC (1x in an adenomacarcinoma of the large intestine, with somatic status) and in InSiGHT Colon Cancer Gene Variant Database (LOVD) (2x as a pathogenic germline mutation, in a classical FAP phenotype, and one unknown phenotype). The c.1956C>T variant occurs in the third last base of the exon. This position has been shown to be part of the splicing consensus sequence and variants involving this position sometimes affect splicing. Two of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a difference in splicing and functional studies have demonstrated a splicing defect contradicting, increasing the likelihood this variant has clinical significance. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 15, 2024