NM_000038.6(APC):c.5981A>T (p.Asp1994Val) AND Familial adenomatous polyposis 1

Clinical significance:Uncertain significance (Last evaluated: Oct 5, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000227428.8

Allele description [Variation Report for NM_000038.6(APC):c.5981A>T (p.Asp1994Val)]

NM_000038.6(APC):c.5981A>T (p.Asp1994Val)

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.5981A>T (p.Asp1994Val)
HGVS:
  • NC_000005.10:g.112841575A>T
  • NG_008481.4:g.154055A>T
  • NM_000038.6:c.5981A>TMANE SELECT
  • NM_001127510.3:c.5981A>T
  • NM_001127511.3:c.5927A>T
  • NM_001354895.2:c.5981A>T
  • NM_001354896.2:c.6035A>T
  • NM_001354897.2:c.6011A>T
  • NM_001354898.2:c.5906A>T
  • NM_001354899.2:c.5897A>T
  • NM_001354900.2:c.5858A>T
  • NM_001354901.2:c.5804A>T
  • NM_001354902.2:c.5708A>T
  • NM_001354903.2:c.5678A>T
  • NM_001354904.2:c.5603A>T
  • NM_001354905.2:c.5501A>T
  • NM_001354906.2:c.5132A>T
  • NP_000029.2:p.Asp1994Val
  • NP_001120982.1:p.Asp1994Val
  • NP_001120983.2:p.Asp1976Val
  • NP_001341824.1:p.Asp1994Val
  • NP_001341825.1:p.Asp2012Val
  • NP_001341826.1:p.Asp2004Val
  • NP_001341827.1:p.Asp1969Val
  • NP_001341828.1:p.Asp1966Val
  • NP_001341829.1:p.Asp1953Val
  • NP_001341830.1:p.Asp1935Val
  • NP_001341831.1:p.Asp1903Val
  • NP_001341832.1:p.Asp1893Val
  • NP_001341833.1:p.Asp1868Val
  • NP_001341834.1:p.Asp1834Val
  • NP_001341835.1:p.Asp1711Val
  • LRG_130:g.154055A>T
  • NC_000005.9:g.112177272A>T
  • NM_000038.5:c.5981A>T
Protein change:
D1711V
Links:
dbSNP: rs774815653
NCBI 1000 Genomes Browser:
rs774815653
Molecular consequence:
  • NM_000038.6:c.5981A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.5981A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.5927A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.5981A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.6035A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.6011A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.5906A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.5897A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.5858A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.5804A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.5708A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.5678A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.5603A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.5501A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.5132A>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000282789Invitaecriteria provided, single submitter
Uncertain significance
(Oct 5, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000785373Counsylcriteria provided, single submitter
Uncertain significance
(Aug 3, 2017)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in Malaysia.

Abdul Murad NA, Othman Z, Khalid M, Abdul Razak Z, Hussain R, Nadesan S, Sagap I, Mohamed Rose I, Wan Ngah WZ, Jamal R.

Dig Dis Sci. 2012 Nov;57(11):2863-72. doi: 10.1007/s10620-012-2240-2. Epub 2012 Jun 6.

PubMed [citation]
PMID:
22669205

Details of each submission

From Invitae, SCV000282789.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces aspartic acid with valine at codon 1994 of the APC protein (p.Asp1994Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs774815653, ExAC 0.009%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 236626). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Counsyl, SCV000785373.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 6, 2021

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