NM_000038.6(APC):c.7657A>C (p.Lys2553Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 20, 2023
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:: RCV001185305.13

Allele description [Variation Report for NM_000038.6(APC):c.7657A>C (p.Lys2553Gln)]

NM_000038.6(APC):c.7657A>C (p.Lys2553Gln)

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.7657A>C (p.Lys2553Gln)

HGVS:

NC_000005.10:g.112843251A>C
NG_008481.4:g.155731A>C
NM_000038.6:c.7657A>CMANE SELECT
NM_001127510.3:c.7657A>C
NM_001127511.3:c.7603A>C
NM_001354895.2:c.7657A>C
NM_001354896.2:c.7711A>C
NM_001354897.2:c.7687A>C
NM_001354898.2:c.7582A>C
NM_001354899.2:c.7573A>C
NM_001354900.2:c.7534A>C
NM_001354901.2:c.7480A>C
NM_001354902.2:c.7384A>C
NM_001354903.2:c.7354A>C
NM_001354904.2:c.7279A>C
NM_001354905.2:c.7177A>C
NM_001354906.2:c.6808A>C
NP_000029.2:p.Lys2553Gln
NP_001120982.1:p.Lys2553Gln
NP_001120983.2:p.Lys2535Gln
NP_001341824.1:p.Lys2553Gln
NP_001341825.1:p.Lys2571Gln
NP_001341826.1:p.Lys2563Gln
NP_001341827.1:p.Lys2528Gln
NP_001341828.1:p.Lys2525Gln
NP_001341829.1:p.Lys2512Gln
NP_001341830.1:p.Lys2494Gln
NP_001341831.1:p.Lys2462Gln
NP_001341832.1:p.Lys2452Gln
NP_001341833.1:p.Lys2427Gln
NP_001341834.1:p.Lys2393Gln
NP_001341835.1:p.Lys2270Gln
LRG_130:g.155731A>C
NC_000005.9:g.112178948A>C
NM_000038.5:c.7657A>C

Protein change:

K2270Q

Links:

dbSNP: rs772318413

NCBI 1000 Genomes Browser:

rs772318413

Molecular consequence:

NM_000038.6:c.7657A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7657A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7603A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7657A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7711A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7687A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7582A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7573A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7534A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7480A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7384A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7354A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7279A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7177A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6808A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Gm29066 AND (alive[prop]) (0)
Gene
CADM1 cell adhesion molecule 1 [Homo sapiens]
CADM1 cell adhesion molecule 1 [Homo sapiens]
Gene ID:23705

Gene
23705[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001351486	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002671797	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 20, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001351486

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 2, 2021)

germline

clinical testing

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

SCV002671797

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 20, 2023)

germline

clinical testing

Citation Link

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

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 Color Diagnostics, LLC DBA Color Health, SCV001351486.2

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

Description

This missense variant replaces lysine with glutamine at codon 2553 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002671797.2

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

Description

The p.K2553Q variant (also known as c.7657A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 7657. The lysine at codon 2553 is replaced by glutamine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

Last Updated: Oct 26, 2024

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