NM_000038.6(APC):c.532-14_532-12del AND Familial adenomatous polyposis 1

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Feb 23, 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:: RCV001353825.17

Allele description [Variation Report for NM_000038.6(APC):c.532-14_532-12del]

NM_000038.6(APC):c.532-14_532-12del

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.532-14_532-12del

HGVS:

NC_000005.10:g.112780773ATT[1]
NG_008481.4:g.93253ATT[1]
NM_000038.6:c.532-14_532-12delMANE SELECT
NM_001127510.3:c.532-14_532-12del
NM_001127511.3:c.562-14_562-12del
NM_001354895.2:c.532-14_532-12del
NM_001354896.2:c.532-14_532-12del
NM_001354897.2:c.562-14_562-12del
NM_001354898.2:c.457-14_457-12del
NM_001354899.2:c.532-14_532-12del
NM_001354900.2:c.355-14_355-12del
NM_001354901.2:c.355-14_355-12del
NM_001354902.2:c.562-14_562-12del
NM_001354903.2:c.532-14_532-12del
NM_001354904.2:c.457-14_457-12del
NM_001354905.2:c.355-14_355-12del
NM_001354906.2:c.-504-14_-504-12del
LRG_130:g.93253ATT[1]
NC_000005.9:g.112116468_112116470del
NC_000005.9:g.112116470ATT[1]
NM_000038.5:c.532-14_532-12delATT

Links:

dbSNP: rs765893314

NCBI 1000 Genomes Browser:

rs765893314

Molecular consequence:

NM_000038.6:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001127510.3:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001127511.3:c.562-14_562-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354895.2:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354896.2:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354897.2:c.562-14_562-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354898.2:c.457-14_457-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354899.2:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354900.2:c.355-14_355-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354901.2:c.355-14_355-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354902.2:c.562-14_562-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354903.2:c.532-14_532-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354904.2:c.457-14_457-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354905.2:c.355-14_355-12del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354906.2:c.-504-14_-504-12del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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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611670 (1)
OMIM
RecName: Full=ATPase family AAA domain-containing protein 3A
RecName: Full=ATPase family AAA domain-containing protein 3A
gi|84028405|sp|Q9NVI7.2|ATD3A_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000591037	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing
SCV002346826	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 13, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004931891	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Feb 23, 2024)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000591037

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

SCV002346826

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 13, 2024)

germline

clinical testing

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

SCV004931891

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely benign
(Feb 23, 2024)

unknown

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
not provided	unknown	yes	1	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

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

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591037.2

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

Description

The c.532-14_532-12del variant has not been previously reported in the literature nor was it identified in public databases. It is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and this variant spans into the -12 position and variants involving these positions sometimes affect splicing. However, splicing prediction softwares (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing, but this information is not predictive enough to rule out pathogenicity. Functional or segregation studies may be required to determine the clinical significance of this variant. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002346826.4

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004931891.1

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

Description

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.

#	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 13, 2024

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