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NM_001048174.2(MUTYH):c.379-3T>C AND Familial adenomatous polyposis 2

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 9, 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:
RCV000524907.8

Allele description [Variation Report for NM_001048174.2(MUTYH):c.379-3T>C]

NM_001048174.2(MUTYH):c.379-3T>C

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.379-3T>C
HGVS:
  • NC_000001.11:g.45332962A>G
  • NG_008189.1:g.12509T>C
  • NM_001048171.2:c.379-3T>C
  • NM_001048172.2:c.382-3T>C
  • NM_001048173.2:c.379-3T>C
  • NM_001048174.2:c.379-3T>CMANE SELECT
  • NM_001128425.2:c.463-3T>C
  • NM_001293190.2:c.424-3T>C
  • NM_001293191.2:c.412-3T>C
  • NM_001293192.2:c.103-3T>C
  • NM_001293195.2:c.379-3T>C
  • NM_001293196.2:c.103-3T>C
  • NM_001350650.2:c.34-3T>C
  • NM_001350651.2:c.34-3T>C
  • NM_012222.3:c.454-3T>C
  • LRG_220t1:c.463-3T>C
  • LRG_220:g.12509T>C
  • NC_000001.10:g.45798634A>G
  • NM_001128425.1:c.463-3T>C
Links:
dbSNP: rs770203030
NCBI 1000 Genomes Browser:
rs770203030
Molecular consequence:
  • NM_001048171.2:c.379-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048172.2:c.382-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048173.2:c.379-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048174.2:c.379-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001128425.2:c.463-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293190.2:c.424-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293191.2:c.412-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293192.2:c.103-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293195.2:c.379-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293196.2:c.103-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350650.2:c.34-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350651.2:c.34-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_012222.3:c.454-3T>C - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000639326Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Oct 9, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004834182All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Aug 15, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000639326.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change falls in intron 5 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs770203030, gnomAD 0.0009%). 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: 464723). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004834182.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This variant causes a T to C nucleotide substitution at the -3 position of intron 5 of the MUTYH gene. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with MUTYH-related disorders in the literature. This variant has been identified in 1/250382 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024