NM_001048174.2(MUTYH):c.1102+1G>A AND Familial adenomatous polyposis 2

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 11, 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:: RCV000503838.15

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1102+1G>A]

NM_001048174.2(MUTYH):c.1102+1G>A

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.1102+1G>A

HGVS:

NC_000001.11:g.45331660C>T
NG_008189.1:g.13811G>A
NM_001048171.2:c.1102+1G>A
NM_001048172.2:c.1105+1G>A
NM_001048173.2:c.1102+1G>A
NM_001048174.2:c.1102+1G>AMANE SELECT
NM_001128425.2:c.1186+1G>A
NM_001293190.2:c.1147+1G>A
NM_001293191.2:c.1135+1G>A
NM_001293192.2:c.826+1G>A
NM_001293195.2:c.1102+1G>A
NM_001293196.2:c.826+1G>A
NM_001350650.2:c.757+1G>A
NM_001350651.2:c.757+1G>A
NM_001407069.1:c.1135+1G>A
NM_001407070.1:c.1102+1G>A
NM_001407071.1:c.1105+1G>A
NM_001407072.1:c.1102+1G>A
NM_001407073.1:c.1102+1G>A
NM_001407075.1:c.1018+1G>A
NM_001407077.1:c.1135+1G>A
NM_001407078.1:c.1105+1G>A
NM_001407079.1:c.1063+1G>A
NM_001407080.1:c.1060+1G>A
NM_001407081.1:c.1102+1G>A
NM_001407082.1:c.757+1G>A
NM_001407083.1:c.1144+1G>A
NM_001407085.1:c.1144+1G>A
NM_001407086.1:c.1105+1G>A
NM_001407087.1:c.1123+1G>A
NM_001407088.1:c.1102+1G>A
NM_001407089.1:c.1102+1G>A
NM_001407091.1:c.826+1G>A
NM_012222.3:c.1177+1G>A
LRG_220t1:c.1186+1G>A
LRG_220:g.13811G>A
NC_000001.10:g.45797332C>T
NM_001128425.1:c.1186+1G>A

Links:

dbSNP: rs587781337

NCBI 1000 Genomes Browser:

rs587781337

Molecular consequence:

NM_001048171.2:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001048172.2:c.1105+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001048173.2:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001048174.2:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001128425.2:c.1186+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001293190.2:c.1147+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001293191.2:c.1135+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001293192.2:c.826+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001293195.2:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001293196.2:c.826+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350650.2:c.757+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350651.2:c.757+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407069.1:c.1135+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407070.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407071.1:c.1105+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407072.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407073.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407075.1:c.1018+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407077.1:c.1135+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407078.1:c.1105+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407079.1:c.1063+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407080.1:c.1060+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407081.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407082.1:c.757+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407083.1:c.1144+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407085.1:c.1144+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407086.1:c.1105+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407087.1:c.1123+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407088.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407089.1:c.1102+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407091.1:c.826+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_012222.3:c.1177+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000941079	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 17, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16134147, 16941501, 17949294, 20848659, 23322991, 25820570, 28492532
SCV002017825	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 17, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004826232	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 11, 2024)	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

SCV000941079

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 17, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002017825

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 17, 2019)

germline

clinical testing

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

SCV004826232

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 11, 2024)

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

Citations

PubMed

Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.

Aceto G, Curia MC, Veschi S, De Lellis L, Mammarella S, Catalano T, Stuppia L, Palka G, Valanzano R, Tonelli F, Casale V, Stigliano V, Cetta F, Battista P, Mariani-Costantini R, Cama A.

Hum Mutat. 2005 Oct;26(4):394.

PubMed [citation]

PMID:: 16134147

Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis.

Lejeune S, Guillemot F, Triboulet JP, Cattan S, Mouton C; PAFNORD Group., Porchet N, Manouvrier S, Buisine MP.

Hum Mutat. 2006 Oct;27(10):1064.

PubMed [citation]

PMID:: 16941501

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000941079.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects a donor splice site in intron 12 of the MUTYH gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs587781337, gnomAD 0.003%). 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: 140874). Studies have shown that disruption of this splice site results in skipping of exon 12, but is expected to preserve the integrity of the reading-frame (Invitae). This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Leu388Pro) have been determined to be pathogenic (PMID: 16134147, 16941501, 17949294, 20848659, 23322991, 25820570). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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 Revvity Omics, Revvity, SCV002017825.3

#	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 All of Us Research Program, National Institutes of Health, SCV004826232.1

#	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: Nov 10, 2024

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