NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter) AND Familial adenomatous polyposis 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 6, 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:: RCV000527702.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter)]

NM_001048174.2(MUTYH):c.856C>T (p.Gln286Ter)

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.856C>T (p.Gln286Ter)

HGVS:

NC_000001.11:g.45332080G>A
NG_008189.1:g.13391C>T
NM_001048171.2:c.856C>T
NM_001048172.2:c.859C>T
NM_001048173.2:c.856C>T
NM_001048174.2:c.856C>TMANE SELECT
NM_001128425.2:c.940C>T
NM_001293190.2:c.901C>T
NM_001293191.2:c.889C>T
NM_001293192.2:c.580C>T
NM_001293195.2:c.856C>T
NM_001293196.2:c.580C>T
NM_001350650.2:c.511C>T
NM_001350651.2:c.511C>T
NM_012222.3:c.931C>T
NP_001041636.2:p.Gln286Ter
NP_001041637.1:p.Gln287Ter
NP_001041638.1:p.Gln286Ter
NP_001041639.1:p.Gln286Ter
NP_001121897.1:p.Gln314Ter
NP_001121897.1:p.Gln314Ter
NP_001280119.1:p.Gln301Ter
NP_001280120.1:p.Gln297Ter
NP_001280121.1:p.Gln194Ter
NP_001280124.1:p.Gln286Ter
NP_001280125.1:p.Gln194Ter
NP_001337579.1:p.Gln171Ter
NP_001337580.1:p.Gln171Ter
NP_036354.1:p.Gln311Ter
LRG_220t1:c.940C>T
LRG_220:g.13391C>T
LRG_220p1:p.Gln314Ter
NC_000001.10:g.45797752G>A
NM_001128425.1:c.940C>T
NR_146882.2:n.1084C>T
NR_146883.2:n.933C>T
p.Q314*

Protein change:

Q171*

Links:

dbSNP: rs587781338

NCBI 1000 Genomes Browser:

rs587781338

Molecular consequence:

NR_146882.2:n.1084C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.933C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048172.2:c.859C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048173.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001048174.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001128425.2:c.940C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293190.2:c.901C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293191.2:c.889C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293192.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293195.2:c.856C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001293196.2:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350650.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001350651.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_012222.3:c.931C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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Mus musculus adult male liver cDNA, RIKEN full-length enriched library, clone:13...
Mus musculus adult male liver cDNA, RIKEN full-length enriched library, clone:1300002E11 product:unclassifiable, full insert sequence
gi|12836345|dbj|AK004850.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000639366	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 6, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18534194, 20663686, 15635083, 24556621, 28492532
SCV004198969	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2023)	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

SCV000639366

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 6, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004198969

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 16, 2023)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

MUTYH-associated polyposis (MAP).

Nielsen M, Morreau H, Vasen HF, Hes FJ.

Crit Rev Oncol Hematol. 2011 Jul;79(1):1-16. doi: 10.1016/j.critrevonc.2010.05.011. Epub 2010 Jul 21. Review.

PubMed [citation]

PMID:: 20663686

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000639366.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gln314*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is present in population databases (rs587781338, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with a personal and family history of prostate cancer and MUTYH-associated polyposis (PMID: 15635083, 24556621). This variant is also known as Y165C. ClinVar contains an entry for this variant (Variation ID: 140876). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as 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, SCV004198969.1

#	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: Sep 29, 2024

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