NM_001048174.2(MUTYH):c.1556del (p.Ala519fs) AND MYH-associated polyposis

Clinical significance:Uncertain significance (Last evaluated: Sep 11, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000200142.5

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1556del (p.Ala519fs)]

NM_001048174.2(MUTYH):c.1556del (p.Ala519fs)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.1556del (p.Ala519fs)
HGVS:
  • NC_000001.11:g.45329316del
  • NG_008189.1:g.16155del
  • NM_001048171.2:c.1556del
  • NM_001048172.2:c.1559del
  • NM_001048173.2:c.1556del
  • NM_001048174.2:c.1556delMANE SELECT
  • NM_001128425.2:c.1640del
  • NM_001293190.2:c.1601del
  • NM_001293191.2:c.1589del
  • NM_001293192.2:c.1280del
  • NM_001293195.2:c.1556del
  • NM_001293196.2:c.1280del
  • NM_001350650.2:c.1211del
  • NM_001350651.2:c.1211del
  • NM_012222.3:c.1631del
  • NP_001041636.2:p.Ala519fs
  • NP_001041637.1:p.Ala520fs
  • NP_001041638.1:p.Ala519fs
  • NP_001041639.1:p.Ala519fs
  • NP_001121897.1:p.Ala547fs
  • NP_001121897.1:p.Ala547fs
  • NP_001280119.1:p.Ala534fs
  • NP_001280120.1:p.Ala530fs
  • NP_001280121.1:p.Ala427fs
  • NP_001280124.1:p.Ala519fs
  • NP_001280125.1:p.Ala427fs
  • NP_001337579.1:p.Ala404fs
  • NP_001337580.1:p.Ala404fs
  • NP_036354.1:p.Ala544fs
  • LRG_220t1:c.1640del
  • LRG_220:g.16155del
  • LRG_220p1:p.Ala547fs
  • NC_000001.10:g.45794988del
  • NM_001048171.1:c.1598delC
  • NM_001128425.1:c.1640del
  • NM_001128425.1:c.1640delC
  • NR_146882.2:n.1964del
  • NR_146883.2:n.1813del
  • p.A547EfsX24
Protein change:
A404fs
Links:
dbSNP: rs587780086
NCBI 1000 Genomes Browser:
rs587780086
Molecular consequence:
  • NM_001048171.2:c.1556del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001048172.2:c.1559del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001048173.2:c.1556del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001048174.2:c.1556del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001128425.2:c.1640del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001293190.2:c.1601del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001293191.2:c.1589del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001293192.2:c.1280del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001293195.2:c.1556del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001293196.2:c.1280del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350650.2:c.1211del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350651.2:c.1211del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_012222.3:c.1631del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_146882.2:n.1964del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.1813del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
MYH-associated polyposis (FAP2)
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; FAP type 2; 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
SCV000253864Invitaecriteria provided, single submitter
Uncertain significance
(Sep 11, 2020)
germlineclinical testing

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

SCV000487313Counsylcriteria provided, single submitter
Uncertain significance
(Nov 20, 2015)
unknownclinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000253864.5

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

Description

This sequence change results in a frameshift in the MUTYH gene (p.Ala547Glufs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acids of the MUTYH protein and extend the protein by an additional 20 amino acids. This variant is present in population databases (rs587780086, ExAC 0.001%). This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 127843). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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 Counsyl, SCV000487313.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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