NM_001048174.2(MUTYH):c.263G>A (p.Arg88Gln) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 31, 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:: RCV000197990.13

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:: 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

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
SCV000254710	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001481307	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 4, 2020)	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

SCV000254710

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

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

SCV001481307

Baylor Genetics - CSER-TexasKidsCanSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 4, 2020)

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	yes	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

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 Invitae, SCV000254710.12

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 116 of the MUTYH protein (p.Arg116Gln). This variant is present in population databases (rs587782683, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. 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: 142736). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV001481307.2

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#	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		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine