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NM_015076.5(CDK19):c.586A>G (p.Thr196Ala) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 8, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002560185.2

Allele description [Variation Report for NM_015076.5(CDK19):c.586A>G (p.Thr196Ala)]

NM_015076.5(CDK19):c.586A>G (p.Thr196Ala)

Gene:
CDK19:cyclin dependent kinase 19 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q21
Genomic location:
Preferred name:
NM_015076.5(CDK19):c.586A>G (p.Thr196Ala)
HGVS:
  • NC_000006.12:g.110632090T>C
  • NM_001300960.2:c.515-4945A>G
  • NM_001300963.2:c.406A>G
  • NM_001300964.2:c.406A>G
  • NM_015076.3:c.586A>G
  • NM_015076.5:c.586A>GMANE SELECT
  • NP_001287892.1:p.Thr136Ala
  • NP_001287893.1:p.Thr136Ala
  • NP_055891.1:p.Thr196Ala
  • NC_000006.11:g.110953293T>C
  • NM_015076.4:c.586A>G
  • p.T196A
Protein change:
T136A; THR196ALA
Links:
OMIM: 614720.0001; dbSNP: rs1779473650
NCBI 1000 Genomes Browser:
rs1779473650
Molecular consequence:
  • NM_001300960.2:c.515-4945A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300963.2:c.406A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001300964.2:c.406A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015076.5:c.586A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003544628Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(Oct 8, 2021)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy.

Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfeld JA, Burrage LC, Liu P, Murdock DR, Yamamoto S, Wangler MF; Undiagnosed Diseases Network., Chao HT, Long H, Feng L, Bacino CA, Bellen HJ, Xiao B.

Am J Hum Genet. 2020 May 7;106(5):717-725. doi: 10.1016/j.ajhg.2020.04.001. Epub 2020 Apr 23.

PubMed [citation]
PMID:
32330417
PMCID:
PMC7212481

Details of each submission

From Ambry Genetics, SCV003544628.2

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

Description

The c.586A>G (p.T196A) alteration is located in exon 6 (coding exon 6) of the CDK19 gene. This alteration results from an A to G substitution at nucleotide position 586, causing the threonine (T) at amino acid position 196 to be replaced by an alanine (A). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported de novo in two unrelated patients with a neurodevelopmental disorder with features including developmental delay, intellectual disability, epilepsy, hypotonia, autistic features, and abnormal brain MRI (Chung, 2020). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Functional studies using flies have shown that loss of Cdk8, the fly homolog of CDK19, causes larval lethality, which is suppressed by expression of human CDK19 reference cDNA. In contrast, the CDK19 p.T196A variant fails to rescue the loss of Cdk8 and behaves as a null allele (Chung, 2020). The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: May 19, 2024