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NM_000038.6(APC):c.5839A>G (p.Thr1947Ala) AND Familial adenomatous polyposis 1

Germline classification:
Uncertain significance (4 submissions)
Last evaluated:
Mar 18, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000206414.21

Allele description [Variation Report for NM_000038.6(APC):c.5839A>G (p.Thr1947Ala)]

NM_000038.6(APC):c.5839A>G (p.Thr1947Ala)

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.5839A>G (p.Thr1947Ala)
HGVS:
  • NC_000005.10:g.112841433A>G
  • NG_008481.4:g.153913A>G
  • NM_000038.6:c.5839A>GMANE SELECT
  • NM_001127510.3:c.5839A>G
  • NM_001127511.3:c.5785A>G
  • NM_001354895.2:c.5839A>G
  • NM_001354896.2:c.5893A>G
  • NM_001354897.2:c.5869A>G
  • NM_001354898.2:c.5764A>G
  • NM_001354899.2:c.5755A>G
  • NM_001354900.2:c.5716A>G
  • NM_001354901.2:c.5662A>G
  • NM_001354902.2:c.5566A>G
  • NM_001354903.2:c.5536A>G
  • NM_001354904.2:c.5461A>G
  • NM_001354905.2:c.5359A>G
  • NM_001354906.2:c.4990A>G
  • NP_000029.2:p.Thr1947Ala
  • NP_001120982.1:p.Thr1947Ala
  • NP_001120983.2:p.Thr1929Ala
  • NP_001341824.1:p.Thr1947Ala
  • NP_001341825.1:p.Thr1965Ala
  • NP_001341826.1:p.Thr1957Ala
  • NP_001341827.1:p.Thr1922Ala
  • NP_001341828.1:p.Thr1919Ala
  • NP_001341829.1:p.Thr1906Ala
  • NP_001341830.1:p.Thr1888Ala
  • NP_001341831.1:p.Thr1856Ala
  • NP_001341832.1:p.Thr1846Ala
  • NP_001341833.1:p.Thr1821Ala
  • NP_001341834.1:p.Thr1787Ala
  • NP_001341835.1:p.Thr1664Ala
  • LRG_130:g.153913A>G
  • NC_000005.9:g.112177130A>G
  • NM_000038.5:c.5839A>G
  • p.T1947A
Protein change:
T1664A
Links:
dbSNP: rs746346292
NCBI 1000 Genomes Browser:
rs746346292
Molecular consequence:
  • NM_000038.6:c.5839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.5839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.5785A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.5839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.5893A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.5869A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.5764A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.5755A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.5716A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.5662A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.5566A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.5536A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.5461A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.5359A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.4990A>G - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000260610Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 24, 2022) 		germlineclinical testing

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

SCV000487773Counsyl
criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))		Uncertain significance
(Nov 23, 2015) 		unknownclinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004017836Myriad Genetics, Inc.
criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))		Uncertain significance
(Feb 16, 2023) 		unknownclinical testing

Citation Link,

SCV005056017Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 18, 2024) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000260610.11

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

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1947 of the APC protein (p.Thr1947Ala). This variant is present in population databases (rs746346292, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 185103). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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, SCV000487773.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Myriad Genetics, Inc., SCV004017836.1

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

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

From Baylor Genetics, SCV005056017.1

#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: Oct 26, 2024