NM_001048174.2(MUTYH):c.607-2A>T AND Familial adenomatous polyposis 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 19, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001378738.4

Allele description

NM_001048174.2(MUTYH):c.607-2A>T

Gene:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.607-2A>T

HGVS:

NC_000001.11:g.45332490T>A
NG_008189.1:g.12981A>T
NM_001048171.2:c.607-2A>T
NM_001048172.2:c.610-2A>T
NM_001048173.2:c.607-2A>T
NM_001048174.2:c.607-2A>TMANE SELECT
NM_001128425.2:c.691-2A>T
NM_001293190.2:c.652-2A>T
NM_001293191.2:c.640-2A>T
NM_001293192.2:c.331-2A>T
NM_001293195.2:c.607-2A>T
NM_001293196.2:c.331-2A>T
NM_001350650.2:c.262-2A>T
NM_001350651.2:c.262-2A>T
NM_001407069.1:c.640-2A>T
NM_001407070.1:c.607-2A>T
NM_001407071.1:c.610-2A>T
NM_001407072.1:c.607-2A>T
NM_001407073.1:c.607-2A>T
NM_001407075.1:c.523-2A>T
NM_001407077.1:c.640-2A>T
NM_001407078.1:c.610-2A>T
NM_001407079.1:c.568-2A>T
NM_001407080.1:c.565-2A>T
NM_001407081.1:c.607-2A>T
NM_001407082.1:c.262-2A>T
NM_001407083.1:c.649-2A>T
NM_001407085.1:c.649-2A>T
NM_001407086.1:c.610-2A>T
NM_001407087.1:c.628-2A>T
NM_001407088.1:c.607-2A>T
NM_001407089.1:c.607-2A>T
NM_001407091.1:c.331-2A>T
NM_012222.3:c.682-2A>T
LRG_220:g.12981A>T
NC_000001.10:g.45798162T>A

Links:

dbSNP: rs1361763237

NCBI 1000 Genomes Browser:

rs1361763237

Molecular consequence:

NM_001048171.2:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048172.2:c.610-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048173.2:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048174.2:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001128425.2:c.691-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293190.2:c.652-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293191.2:c.640-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293192.2:c.331-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293195.2:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293196.2:c.331-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001350650.2:c.262-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001350651.2:c.262-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407069.1:c.640-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407070.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407071.1:c.610-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407072.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407073.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407075.1:c.523-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407077.1:c.640-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407078.1:c.610-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407079.1:c.568-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407080.1:c.565-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407081.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407082.1:c.262-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407083.1:c.649-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407085.1:c.649-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407086.1:c.610-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407087.1:c.628-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407088.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407089.1:c.607-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407091.1:c.331-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_012222.3:c.682-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Familial adenomatous polyposis 2
Synonyms:: COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576377	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 19, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 18534194, 20663686, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576377

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 19, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Characterization of mutant MUTYH proteins associated with familial colorectal cancer.

Ali M, Kim H, Cleary S, Cupples C, Gallinger S, Bristow R.

Gastroenterology. 2008 Aug;135(2):499-507. doi: 10.1053/j.gastro.2008.04.035. Epub 2008 May 7.

PubMed [citation]

PMID:: 18534194
PMCID:: PMC2761659

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001576377.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant has not been reported in the literature in individuals with MUTYH-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 8 of the MUTYH gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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: Feb 14, 2024

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