U.S. flag

An official website of the United States government

NM_001048174.2(MUTYH):c.420+19_420+31del AND Familial adenomatous polyposis 2

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Nov 19, 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:
RCV000459179.16

Allele description [Variation Report for NM_001048174.2(MUTYH):c.420+19_420+31del]

NM_001048174.2(MUTYH):c.420+19_420+31del

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.420+19_420+31del
HGVS:
  • NC_000001.10:g.45798561_45798573delTATTTCCCCTACC
  • NC_000001.11:g.45332889_45332901del
  • NG_008189.1:g.12572_12584del
  • NM_001048171.2:c.420+19_420+31del
  • NM_001048172.2:c.423+19_423+31del
  • NM_001048173.2:c.420+19_420+31del
  • NM_001048174.2:c.420+19_420+31delMANE SELECT
  • NM_001128425.2:c.504+19_504+31del
  • NM_001293190.2:c.465+19_465+31del
  • NM_001293191.2:c.453+19_453+31del
  • NM_001293192.2:c.144+19_144+31del
  • NM_001293195.2:c.420+19_420+31del
  • NM_001293196.2:c.144+19_144+31del
  • NM_001350650.2:c.75+19_75+31del
  • NM_001350651.2:c.75+19_75+31del
  • NM_012222.3:c.495+19_495+31del
  • LRG_220t1:c.504+19_504+31del
  • LRG_220:g.12572_12584del
  • NC_000001.10:g.45798559_45798571del
  • NC_000001.10:g.45798561_45798573del
  • NC_000001.10:g.45798561_45798573del
  • NC_000001.10:g.45798561_45798573delTATTTCCCCTACC
  • NM_001048174.2:c.420+19_420+31del
  • NM_001128425.1:c.504+19_504+31del
  • NM_001128425.1:c.504+19_504+31del
  • NM_001128425.1:c.504+19_504+31delTAGGGGAAATAGG
  • NM_001128425.2:c.504+19_504+31del
Links:
dbSNP: rs781222233
NCBI 1000 Genomes Browser:
rs781222233
Molecular consequence:
  • NM_001048171.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048172.2:c.423+19_423+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048173.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001048174.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001128425.2:c.504+19_504+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293190.2:c.465+19_465+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293191.2:c.453+19_453+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293192.2:c.144+19_144+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293195.2:c.420+19_420+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001293196.2:c.144+19_144+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350650.2:c.75+19_75+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350651.2:c.75+19_75+31del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_012222.3:c.495+19_495+31del - intron variant - [Sequence Ontology: SO:0001627]
Observations:
3

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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000545720Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 19, 2024)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV000799495Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))
Likely pathogenic
(Apr 23, 2018)
unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV004198977Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 17, 2023)
unknownclinical testing

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

SCV004815007All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely Pathogenic
(Jun 26, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]
PMID:
21520333

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
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000545720.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change falls in intron 6 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs781222233, gnomAD 0.002%). This variant has been observed in individual(s) with MUTYH-associated polyposis (PMID: 16890597, 19732775, 20628285, 21520333). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as IVS6+19-31del13. ClinVar contains an entry for this variant (Variation ID: 406825). Studies have shown that this variant results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 20628285; internal data). For these reasons, this variant has been classified as Pathogenic.

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

From Counsyl, SCV000799495.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004198977.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004815007.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (7)

Description

This variant causes a 13 base pair deletion in intron 6 of the MUTYH gene. An RNA study found this variant resulted in the in-frame skipping of exon 6 (PMID: 20628285). This variant has been reported in compound heterozygous and homozygous carriers with polyposis and/or colorectal cancer (PMID: 16890597, 19732775, 20618354, 20628285, 26446593, 27829682). In particular, this variant was observed in the compound heterozygous state with a pathogenic variant, c.1437_1439del, in an individual affected with polyps and colorectal cancer (PMID: 20628285). The proband's mother, who was heterozygous for this variant, as well as the proband's sister, who was heterozygous for c.1437_1439del variant, were unaffected with polyps and colorectal cancer. This variant was also observed in homozygosity in three siblings in a different family (PMID: 20628285). Their heterozygous mother, father, and one sibling were unaffected with polyps and colorectal cancer (PMID: 20628285). This variant has been identified in 2/251048 chromosomes 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided3not providednot providednot provided

Last Updated: Feb 16, 2025