NM_001048174.2(MUTYH):c.36C>T (p.His12=) AND Familial adenomatous polyposis 2

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jan 10, 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:: RCV000233690.15

Allele description [Variation Report for NM_001048174.2(MUTYH):c.36C>T (p.His12=)]

NM_001048174.2(MUTYH):c.36C>T (p.His12=)

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.36C>T (p.His12=)

HGVS:

NC_000001.11:g.45334470G>A
NG_008189.1:g.11001C>T
NM_001048171.2:c.36C>T
NM_001048172.2:c.36C>T
NM_001048173.2:c.36C>T
NM_001048174.2:c.36C>TMANE SELECT
NM_001128425.2:c.78C>T
NM_001293190.2:c.78C>T
NM_001293191.2:c.36C>T
NM_001293192.2:c.-177C>T
NM_001293195.2:c.36C>T
NM_001293196.2:c.-177C>T
NM_001350650.2:c.-236C>T
NM_001350651.2:c.-172C>T
NM_012222.3:c.78C>T
NP_001041636.2:p.His12=
NP_001041637.1:p.His12=
NP_001041638.1:p.His12=
NP_001041639.1:p.His12=
NP_001121897.1:p.His26=
NP_001121897.1:p.His26=
NP_001280119.1:p.His26=
NP_001280120.1:p.His12=
NP_001280124.1:p.His12=
NP_036354.1:p.His26=
LRG_220t1:c.78C>T
LRG_220:g.11001C>T
LRG_220p1:p.His26=
NC_000001.10:g.45800142G>A
NM_001128425.1:c.78C>T
NR_146882.2:n.264C>T
NR_146883.2:n.187C>T
p.H26H

Links:

dbSNP: rs776396492

NCBI 1000 Genomes Browser:

rs776396492

Molecular consequence:

NM_001293192.2:c.-177C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-177C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-236C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-172C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_146882.2:n.264C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.187C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001048171.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001048172.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001048173.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001048174.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001128425.2:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001293190.2:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001293191.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001293195.2:c.36C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_012222.3:c.78C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

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

gp084 [Erwinia phage vB_EamP-S6]
gp084 [Erwinia phage vB_EamP-S6]
gi|422935923|ref|YP_007005820.1|

Protein

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
SCV000285965	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 10, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001548594	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely benign	unknown	clinical testing
SCV004835682	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Nov 30, 2023)	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

SCV000285965

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 10, 2024)

germline

clinical testing

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

SCV001548594

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Likely benign

unknown

clinical testing

SCV004835682

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Nov 30, 2023)

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	3	not provided	not provided	108544	not provided	clinical testing
not provided	unknown	yes	1	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, SCV000285965.9

#	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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001548594.1

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

Description

The MUTYH p.His26= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, or UMD-LSDB, databases. The variant was identified in dbSNP (ID: rs776396492) as "With Likely benign allele ", and in ClinVar (classified as likely benign by Ambry Genetics, Invitae, Color Genomics). The variant was identified in control databases in 2 of 246264 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in East Asian population in 2 of 17248 chromosomes (freq: 0.000116), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, Finnish, and South Asian populations. The p.His26= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

#	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		1	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004835682.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine