NM_001048174.2(MUTYH):c.1102+1G>T AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 28, 2022
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:: RCV000582433.8

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

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

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>T

HGVS:

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

Links:

dbSNP: rs587781337

NCBI 1000 Genomes Browser:

rs587781337

Molecular consequence:

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

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000690502	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001170373	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jul 16, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000690502

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 28, 2022)

germline

clinical testing

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

SCV001170373

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jul 16, 2019)

germline

clinical testing

Citation Link

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

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 Color Diagnostics, LLC DBA Color Health, SCV000690502.4

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

Description

This variant causes a G to T nucleotide substitution at the +1 position of intron 12 of the MUTYH gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely 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 Ambry Genetics, SCV001170373.4

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

Description

The c.1186+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 12 of the MUTYH gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely 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

Last Updated: Sep 29, 2024

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