NM_001048174.2(MUTYH):c.1393-1G>A AND Familial adenomatous polyposis 2

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 7, 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:: RCV000410065.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1393-1G>A]

NM_001048174.2(MUTYH):c.1393-1G>A

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.1393-1G>A

HGVS:

NC_000001.11:g.45330558C>T
NG_008189.1:g.14913G>A
NM_001048171.2:c.1393-1G>A
NM_001048172.2:c.1396-1G>A
NM_001048173.2:c.1393-1G>A
NM_001048174.2:c.1393-1G>AMANE SELECT
NM_001128425.2:c.1477-1G>A
NM_001293190.2:c.1438-1G>A
NM_001293191.2:c.1426-1G>A
NM_001293192.2:c.1117-1G>A
NM_001293195.2:c.1393-1G>A
NM_001293196.2:c.1117-1G>A
NM_001350650.2:c.1048-1G>A
NM_001350651.2:c.1048-1G>A
NM_001407069.1:c.1426-1G>A
NM_001407070.1:c.1393-1G>A
NM_001407071.1:c.1396-1G>A
NM_001407072.1:c.1393-1G>A
NM_001407073.1:c.1393-1G>A
NM_001407075.1:c.1309-1G>A
NM_001407077.1:c.1426-1G>A
NM_001407078.1:c.1396-1G>A
NM_001407079.1:c.1354-1G>A
NM_001407080.1:c.1351-1G>A
NM_001407081.1:c.1393-1G>A
NM_001407082.1:c.1048-1G>A
NM_001407083.1:c.1435-1G>A
NM_001407085.1:c.1435-1G>A
NM_001407086.1:c.1396-1G>A
NM_001407087.1:c.1414-1G>A
NM_001407088.1:c.1393-1G>A
NM_001407089.1:c.1393-1G>A
NM_001407091.1:c.1117-1G>A
NM_012222.3:c.1468-1G>A
LRG_220t1:c.1477-1G>A
LRG_220:g.14913G>A
NC_000001.10:g.45796230C>T
NM_001048171.1:c.1435-1G>A
NM_001128425.1:c.1477-1G>A

Links:

dbSNP: rs1057517459

NCBI 1000 Genomes Browser:

rs1057517459

Molecular consequence:

NM_001048171.2:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048172.2:c.1396-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048173.2:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001048174.2:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001128425.2:c.1477-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293190.2:c.1438-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293191.2:c.1426-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293192.2:c.1117-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293195.2:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001293196.2:c.1117-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001350650.2:c.1048-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001350651.2:c.1048-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407069.1:c.1426-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407070.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407071.1:c.1396-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407072.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407073.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407075.1:c.1309-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407077.1:c.1426-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407078.1:c.1396-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407079.1:c.1354-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407080.1:c.1351-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407081.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407082.1:c.1048-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407083.1:c.1435-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407085.1:c.1435-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407086.1:c.1396-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407087.1:c.1414-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407088.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407089.1:c.1393-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407091.1:c.1117-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_012222.3:c.1468-1G>A - 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
SCV000487375	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Aug 15, 2016)	unknown	clinical testing	mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV001390430	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 12, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 18534194, 20663686, 28492532
SCV005056040	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 7, 2024)	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

SCV000487375

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Aug 15, 2016)

unknown

clinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001390430

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 12, 2024)

germline

clinical testing

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

SCV005056040

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 7, 2024)

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

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 (5)

Details of each submission

From Counsyl, SCV000487375.2

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001390430.6

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

Description

This sequence change affects an acceptor splice site in intron 14 of the MUTYH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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 is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 371681). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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 Baylor Genetics, SCV005056040.1

#	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: May 16, 2025

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