NM_001048174.2(MUTYH):c.263G>A (p.Arg88Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 6, 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:: RCV000132110.13

Allele description [Variation Report for NM_001048174.2(MUTYH):c.263G>A (p.Arg88Gln)]

NM_001048174.2(MUTYH):c.263G>A (p.Arg88Gln)

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.263G>A (p.Arg88Gln)

HGVS:

NC_000001.11:g.45333414C>T
NG_008189.1:g.12057G>A
NM_001048171.2:c.263G>A
NM_001048172.2:c.266G>A
NM_001048173.2:c.263G>A
NM_001048174.2:c.263G>AMANE SELECT
NM_001128425.2:c.347G>A
NM_001293190.2:c.308G>A
NM_001293191.2:c.296G>A
NM_001293192.2:c.-14G>A
NM_001293195.2:c.263G>A
NM_001293196.2:c.-14G>A
NM_001350650.2:c.-9G>A
NM_001350651.2:c.-9G>A
NM_012222.3:c.338G>A
NP_001041636.2:p.Arg88Gln
NP_001041637.1:p.Arg89Gln
NP_001041638.1:p.Arg88Gln
NP_001041639.1:p.Arg88Gln
NP_001121897.1:p.Arg116Gln
NP_001121897.1:p.Arg116Gln
NP_001280119.1:p.Arg103Gln
NP_001280120.1:p.Arg99Gln
NP_001280124.1:p.Arg88Gln
NP_036354.1:p.Arg113Gln
LRG_220t1:c.347G>A
LRG_220:g.12057G>A
LRG_220p1:p.Arg116Gln
NC_000001.10:g.45799086C>T
NM_001128425.1:c.347G>A
NR_146882.2:n.491G>A
NR_146883.2:n.414G>A
p.R116Q

Protein change:

R103Q

Links:

dbSNP: rs587782683

NCBI 1000 Genomes Browser:

rs587782683

Molecular consequence:

NM_001293192.2:c.-14G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-14G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-9G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-9G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001048171.2:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.266G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.308G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.296G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.338G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.491G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.414G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000187176	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 8, 2023)	germline	clinical testing	Citation Link,
SCV000903449	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 36672847, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000187176

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 8, 2023)

germline

clinical testing

Citation Link,

SCV000903449

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 6, 2023)

germline

clinical testing

PubMed (2)
[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

Frequency of Pathogenic Germline Mutations in Early and Late Onset Familial Breast Cancer Patients Using Multi-Gene Panel Sequencing: An Egyptian Study.

Nassar A, Zekri AN, Kamel MM, Elberry MH, Lotfy MM, Seadawy MG, Hassan ZK, Soliman HK, Lymona AM, Youssef ASE.

Genes (Basel). 2022 Dec 29;14(1). doi:pii: 106. 10.3390/genes14010106.

PubMed [citation]

PMID:: 36672847
PMCID:: PMC9858960

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 Ambry Genetics, SCV000187176.9

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

Description

The p.R116Q variant (also known as c.347G>A), located in coding exon 3 of the MUTYH gene, results from a G to A substitution at nucleotide position 347. The arginine at codon 116 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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

From Color Diagnostics, LLC DBA Color Health, SCV000903449.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces arginine with glutamine at codon 116 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial breast cancer (PMID: 36672847). This variant has been identified in 17/282866 chromosomes 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

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine