NM_001347721.2(DYRK1A):c.638-9_638-5del AND Mental retardation, autosomal dominant 7

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 18, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000576181.4

Allele description [Variation Report for NM_001347721.2(DYRK1A):c.638-9_638-5del]

NM_001347721.2(DYRK1A):c.638-9_638-5del

Gene:
DYRK1A:dual specificity tyrosine phosphorylation regulated kinase 1A [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
21q22.13
Genomic location:
Preferred name:
NM_001347721.2(DYRK1A):c.638-9_638-5del
HGVS:
  • NC_000021.9:g.37490166_37490170del
  • NG_009366.1:g.127610_127614del
  • NM_001347721.2:c.638-9_638-5delMANE SELECT
  • NM_001347722.2:c.638-9_638-5del
  • NM_001347723.2:c.551-9_551-5del
  • NM_001396.5:c.665-9_665-5del
  • NM_101395.2:c.665-9_665-5del
  • NM_130436.2:c.638-9_638-5del
  • NM_130438.2:c.665-9_665-5del
  • NC_000021.8:g.38862468_38862472del
  • NM_001396.3:c.665-9_665-5del
  • NM_001396.3:c.665-9_665-5delCTCTT
  • NM_101395.2:c.665-9_665-5delCTCTT
  • NM_130436.2:c.638-9_638-5delCTCTT
Links:
Molecular consequence:
  • NM_001347721.2:c.638-9_638-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001347722.2:c.638-9_638-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001347723.2:c.551-9_551-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001396.5:c.665-9_665-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_101395.2:c.665-9_665-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130436.2:c.638-9_638-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130438.2:c.665-9_665-5del - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Name:
Mental retardation, autosomal dominant 7 (MRD7)
Synonyms:
DYRK1A-Related Intellectual Disability Syndrome
Identifiers:
MONDO: MONDO:0013578; MedGen: C3279839; OMIM: 614104

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000677027Invitaecriteria provided, single submitter
Pathogenic
(Jan 9, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001423647Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospitalcriteria provided, single submitter
Likely pathogenic
(Jan 18, 2019)
germlineclinical testing

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

SCV001432317Service de Génétique Moléculaire,Hôpital Robert Debréno assertion criteria providedLikely pathogenicunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot provided1not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.

van Bon BW, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, Kleefstra T, Willemsen MH, Kumar R, Bosco P, Fichera M, Li D, Amaral D, Cristofoli F, Peeters H, Haan E, Romano C, Mefford HC, Scheffer I, Gecz J, de Vries BB, Eichler EE.

Mol Psychiatry. 2016 Jan;21(1):126-32. doi: 10.1038/mp.2015.5. Epub 2015 Feb 24.

PubMed [citation]
PMID:
25707398
PMCID:
PMC4547916

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
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000677027.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change falls in intron 5 of the DYRK1A gene. It does not directly change the encoded amino acid sequence of the DYRK1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in 2 individuals affected with DYRK1A-related disease (PMID: 25707398, Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

From Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital, SCV001423647.1

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

Description

[ACMG/AMP: PS2, PM2, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

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

From Service de Génétique Moléculaire,Hôpital Robert Debré, SCV001432317.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot provided1not provided

Last Updated: Nov 27, 2021

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