NM_000038.6(APC):c.6019T>C (p.Tyr2007His) AND Classic or attenuated familial adenomatous polyposis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 29, 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:: RCV004001965.4

Allele description [Variation Report for NM_000038.6(APC):c.6019T>C (p.Tyr2007His)]

NM_000038.6(APC):c.6019T>C (p.Tyr2007His)

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.6019T>C (p.Tyr2007His)

HGVS:

NC_000005.10:g.112841613T>C
NG_008481.4:g.154093T>C
NM_000038.6:c.6019T>CMANE SELECT
NM_001127510.3:c.6019T>C
NM_001127511.3:c.5965T>C
NM_001354895.2:c.6019T>C
NM_001354896.2:c.6073T>C
NM_001354897.2:c.6049T>C
NM_001354898.2:c.5944T>C
NM_001354899.2:c.5935T>C
NM_001354900.2:c.5896T>C
NM_001354901.2:c.5842T>C
NM_001354902.2:c.5746T>C
NM_001354903.2:c.5716T>C
NM_001354904.2:c.5641T>C
NM_001354905.2:c.5539T>C
NM_001354906.2:c.5170T>C
NP_000029.2:p.Tyr2007His
NP_001120982.1:p.Tyr2007His
NP_001120983.2:p.Tyr1989His
NP_001341824.1:p.Tyr2007His
NP_001341825.1:p.Tyr2025His
NP_001341826.1:p.Tyr2017His
NP_001341827.1:p.Tyr1982His
NP_001341828.1:p.Tyr1979His
NP_001341829.1:p.Tyr1966His
NP_001341830.1:p.Tyr1948His
NP_001341831.1:p.Tyr1916His
NP_001341832.1:p.Tyr1906His
NP_001341833.1:p.Tyr1881His
NP_001341834.1:p.Tyr1847His
NP_001341835.1:p.Tyr1724His
LRG_130t1:c.6019T>C
LRG_130:g.154093T>C
NC_000005.9:g.112177310T>C
NM_000038.4:c.6019T>C
NM_000038.5:c.6019T>C

Protein change:

Y1724H

Links:

dbSNP: rs745811356

Molecular consequence:

NM_000038.6:c.6019T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.6019T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.5965T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.6019T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.6073T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.6049T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.5944T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.5935T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.5896T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.5842T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.5746T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.5716T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.5641T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.5539T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.5170T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Classic or attenuated familial adenomatous polyposis
Identifiers:: MONDO: MONDO:0021057; MedGen: CN372698

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004838136	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jul 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005918586	Department of Pathology and Laboratory Medicine, Sinai Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 29, 2023)	germline	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

SCV004838136

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jul 29, 2024)

germline

clinical testing

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

SCV005918586

Department of Pathology and Laboratory Medicine, Sinai Health System

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 29, 2023)

germline

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	11	not provided	not provided	143475	not provided	clinical testing

Citations

PubMed

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 All of Us Research Program, National Institutes of Health, SCV004838136.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	11	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces tyrosine with histidine at codon 2007 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 8/281524 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	143475	not provided	not provided		11	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System, SCV005918586.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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