NM_015076.5(CDK19):c.82G>C (p.Gly28Arg) AND Developmental and epileptic encephalopathy, 87

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 18, 2022
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001252678.11

Allele description [Variation Report for NM_015076.5(CDK19):c.82G>C (p.Gly28Arg)]

NM_015076.5(CDK19):c.82G>C (p.Gly28Arg)

Genes:

AMD1:adenosylmethionine decarboxylase 1 [Gene - OMIM - HGNC]
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.82G>C (p.Gly28Arg)

Other names:

CDK19, GLY28ARG, c.82G-C

HGVS:

NC_000006.12:g.110815055C>G
NG_109014.1:g.592C>G
NM_001287215.2:c.-98+240C>G
NM_001300960.2:c.82G>C
NM_001300963.2:c.-115+516G>C
NM_001300964.2:c.-53+753G>C
NM_015076.5:c.82G>CMANE SELECT
NP_001287889.1:p.Gly28Arg
NP_055891.1:p.Gly28Arg
NC_000006.11:g.111136258C>G
NM_015076.4:c.82G>C

Protein change:

G28R; GLY28ARG

Links:

OMIM: 614720.0004; dbSNP: rs1783519120

NCBI 1000 Genomes Browser:

rs1783519120

Molecular consequence:

NM_001287215.2:c.-98+240C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001300963.2:c.-115+516G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001300964.2:c.-53+753G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001300960.2:c.82G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015076.5:c.82G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental and epileptic encephalopathy, 87
Synonyms:: EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 87
Identifiers:: MONDO: MONDO:0030059; MedGen: C5394501; OMIM: 618916

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001428436	Zarate Arkansas Children's Genetics Clinic, Arkansas Children's Hospital	no assertion criteria provided	Pathogenic (Aug 11, 2020)	de novo	clinical testing
SCV002584926	OMIM	no assertion criteria provided	Pathogenic (Oct 18, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001428436

Zarate Arkansas Children's Genetics Clinic, Arkansas Children's Hospital

no assertion criteria provided

Pathogenic
(Aug 11, 2020)

de novo

clinical testing

SCV002584926

OMIM

no assertion criteria provided

Pathogenic
(Oct 18, 2022)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Zarate YA, Uehara T, Abe K, Oginuma M, Harako S, Ishitani S, Lehesjoki AE, Bierhals T, Kloth K, Ehmke N, Horn D, Holtgrewe M, Anderson K, Viskochil D, Edgar-Zarate CL, Sacoto MJG, Schnur RE, Morrow MM, Sanchez-Valle A, Pappas J, Rabin R, Muona M, et al.

Genet Med. 2021 Jun;23(6):1050-1057. doi: 10.1038/s41436-020-01091-9. Epub 2021 Jan 25.

PubMed [citation]

PMID:: 33495529

Details of each submission

From Zarate Arkansas Children's Genetics Clinic, Arkansas Children's Hospital, SCV001428436.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

De novo variant, in conserved residue, absent in population databases, located in functional domain with other variants, functional studies demonstrate a damaging effect with reduced kinase activity compared to WT, other individuals with same substitution

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

From OMIM, SCV002584926.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Among 11 unrelated patients with developmental and epileptic encephalopathy-87 (DEE87; 618916), Zarate et al. (2021) reported 4 patients with a gly28-to-arg substitution (G28R) in the CDK19 gene, 2 due to a G-C transversion (c.82G-C) and 2 due to a G-A transition (c.82G-A; 614720.0005). Phosphorylation assays showed that kinase activity was lower for the G28R protein compared to wildtype protein activity. Injection of G28R CDK19 mRNA into a zebrafish model significantly increased the percentage of embryos with morphologic abnormalities compared to injection with wildtype CDK19 mRNA.

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

Last Updated: Oct 26, 2024

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