NM_001048174.2(MUTYH):c.200C>A (p.Ala67Asp) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 27, 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:: RCV003096091.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.200C>A (p.Ala67Asp)]

NM_001048174.2(MUTYH):c.200C>A (p.Ala67Asp)

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.200C>A (p.Ala67Asp)

HGVS:

NC_000001.11:g.45333477G>T
NG_008189.1:g.11994C>A
NM_001048171.2:c.200C>A
NM_001048172.2:c.203C>A
NM_001048173.2:c.200C>A
NM_001048174.2:c.200C>AMANE SELECT
NM_001128425.2:c.284C>A
NM_001293190.2:c.245C>A
NM_001293191.2:c.233C>A
NM_001293192.2:c.-77C>A
NM_001293195.2:c.200C>A
NM_001293196.2:c.-77C>A
NM_001350650.2:c.-72C>A
NM_001350651.2:c.-72C>A
NM_012222.3:c.275C>A
NP_001041636.2:p.Ala67Asp
NP_001041637.1:p.Ala68Asp
NP_001041638.1:p.Ala67Asp
NP_001041639.1:p.Ala67Asp
NP_001121897.1:p.Ala95Asp
NP_001280119.1:p.Ala82Asp
NP_001280120.1:p.Ala78Asp
NP_001280124.1:p.Ala67Asp
NP_036354.1:p.Ala92Asp
LRG_220:g.11994C>A
NC_000001.10:g.45799149G>T
NM_001128425.1:c.284C>A
NR_146882.2:n.428C>A
NR_146883.2:n.351C>A

Protein change:

A67D

Links:

dbSNP: rs1645363196

NCBI 1000 Genomes Browser:

rs1645363196

Molecular consequence:

NM_001293192.2:c.-77C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-77C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-72C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-72C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001048171.2:c.200C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.203C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.200C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.200C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.284C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.245C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.233C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.200C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.275C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.428C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.351C>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
SCV003521781	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003817135	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 1, 2022)	germline	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

SCV003521781

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 2023)

germline

clinical testing

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

SCV003817135

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 1, 2022)

germline

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003521781.2

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

Description

ClinVar contains an entry for this variant (Variation ID: 1697954). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 95 of the MUTYH protein (p.Ala95Asp).

#	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 Revvity Omics, Revvity, SCV003817135.2

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine