NM_000038.6(APC):c.7540A>G (p.Thr2514Ala) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 15, 2021
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:: RCV001778967.10

Allele description [Variation Report for NM_000038.6(APC):c.7540A>G (p.Thr2514Ala)]

NM_000038.6(APC):c.7540A>G (p.Thr2514Ala)

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.7540A>G (p.Thr2514Ala)

HGVS:

NC_000005.10:g.112843134A>G
NG_008481.4:g.155614A>G
NM_000038.6:c.7540A>GMANE SELECT
NM_001127510.3:c.7540A>G
NM_001127511.3:c.7486A>G
NM_001354895.2:c.7540A>G
NM_001354896.2:c.7594A>G
NM_001354897.2:c.7570A>G
NM_001354898.2:c.7465A>G
NM_001354899.2:c.7456A>G
NM_001354900.2:c.7417A>G
NM_001354901.2:c.7363A>G
NM_001354902.2:c.7267A>G
NM_001354903.2:c.7237A>G
NM_001354904.2:c.7162A>G
NM_001354905.2:c.7060A>G
NM_001354906.2:c.6691A>G
NP_000029.2:p.Thr2514Ala
NP_001120982.1:p.Thr2514Ala
NP_001120983.2:p.Thr2496Ala
NP_001341824.1:p.Thr2514Ala
NP_001341825.1:p.Thr2532Ala
NP_001341826.1:p.Thr2524Ala
NP_001341827.1:p.Thr2489Ala
NP_001341828.1:p.Thr2486Ala
NP_001341829.1:p.Thr2473Ala
NP_001341830.1:p.Thr2455Ala
NP_001341831.1:p.Thr2423Ala
NP_001341832.1:p.Thr2413Ala
NP_001341833.1:p.Thr2388Ala
NP_001341834.1:p.Thr2354Ala
NP_001341835.1:p.Thr2231Ala
LRG_130:g.155614A>G
NC_000005.9:g.112178831A>G
NM_000038.5:c.7540A>G

Protein change:

T2231A

Links:

dbSNP: rs545125246

NCBI 1000 Genomes Browser:

rs545125246

Molecular consequence:

NM_000038.6:c.7540A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7540A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7486A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7540A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7594A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7570A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7465A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7456A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7417A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7363A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7267A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7162A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7060A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6691A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002014914	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002046246	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Sep 23, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002014914

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 15, 2021)

germline

clinical testing

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

Citation Link,

SCV002046246

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Sep 23, 2020)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

George SHL, Donenberg T, Alexis C, DeGennaro V Jr, Dyer H, Yin S, Ali J, Butler R, Chin SN, Curling D, Lowe D, Lunn J, Turnquest T, Wharfe G, Cerbon D, Barreto-Coelho P, Schlumbrecht MP, Akbari MR, Narod SA, Hurley JE.

JAMA Netw Open. 2021 Mar 1;4(3):e210307. doi: 10.1001/jamanetworkopen.2021.0307.

PubMed [citation]

PMID:: 33646313
PMCID:: PMC7921902

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002014914.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: APC c.7540A>G (p.Thr2514Ala) results in a non-conservative amino acid change located in the Adenomatous polyposis coli protein basic domain (IPR009234) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251098 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge c.7540A>G has not been reported in the literature in individuals affected with Familial Adenomatous Polyposis. At least one individual affected with breast cancer has been identifeid with this variant (George_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046246.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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