NM_001347721.2(DYRK1A):c.545_548del (p.Lys182fs) AND DYRK1A-related intellectual disability syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 24, 2021
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:: RCV001251101.4

Allele description

NM_001347721.2(DYRK1A):c.545_548del (p.Lys182fs)

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.545_548del (p.Lys182fs)

HGVS:

NC_000021.9:g.37486522_37486525del
NG_009366.1:g.123966_123969del
NM_001347721.2:c.545_548delMANE SELECT
NM_001347722.2:c.545_548del
NM_001347723.2:c.458_461del
NM_001396.5:c.572_575del
NM_101395.2:c.572_575del
NM_130436.2:c.545_548del
NM_130438.2:c.572_575del
NP_001334650.1:p.Lys182fs
NP_001334651.1:p.Lys182fs
NP_001334652.1:p.Lys153fs
NP_001387.2:p.Lys191fs
NP_567824.1:p.Lys191fs
NP_569120.1:p.Lys182fs
NP_569122.1:p.Lys191fs
NC_000021.8:g.38858822_38858825del
NC_000021.8:g.38858824_38858827del
NM_001396.3:c.572_575del
NM_001396.3:c.572_575delAGAA

Protein change:

K153fs

Links:

dbSNP: rs1064796367

NCBI 1000 Genomes Browser:

rs1064796367

Molecular consequence:

NM_001347721.2:c.545_548del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347722.2:c.545_548del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001347723.2:c.458_461del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001396.5:c.572_575del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_101395.2:c.572_575del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130436.2:c.545_548del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_130438.2:c.572_575del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: DYRK1A-related intellectual disability syndrome (MRD7)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 7
Identifiers:: MONDO: MONDO:0013578; MedGen: C5568143; OMIM: 614104

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001426600	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 32860008
SCV002238504	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32860008, 25944381, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001426600

Centogene AG - the Rare Disease Company

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

de novo

clinical testing

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

SCV002238504

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 24, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort.

Bertoli-Avella AM, Beetz C, Ameziane N, Rocha ME, Guatibonza P, Pereira C, Calvo M, Herrera-Ordonez N, Segura-Castel M, Diego-Alvarez D, Zawada M, Kandaswamy KK, Werber M, Paknia O, Zielske S, Ugrinovski D, Warnack G, Kampe K, Iurașcu MI, Cozma C, Vogel F, Alhashem A, et al.

Eur J Hum Genet. 2021 Jan;29(1):141-153. doi: 10.1038/s41431-020-00713-9. Epub 2020 Aug 28.

PubMed [citation]

PMID:: 32860008
PMCID:: PMC7852664

See all PubMed Citations (4)

Details of each submission

From Centogene AG - the Rare Disease Company, SCV001426600.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002238504.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 423335). This premature translational stop signal has been observed in individual(s) with clinical features of DYRK1A-related conditions (PMID: 32860008). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys191Thrfs*6) in the DYRK1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYRK1A are known to be pathogenic (PMID: 25944381).

#	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: Aug 4, 2024

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