NM_015076.5(CDK19):c.92C>A (p.Thr31Asn) AND Developmental and epileptic encephalopathy, 87

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 4, 2022
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:: RCV001250507.11

Allele description [Variation Report for NM_015076.5(CDK19):c.92C>A (p.Thr31Asn)]

NM_015076.5(CDK19):c.92C>A (p.Thr31Asn)

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.92C>A (p.Thr31Asn)

HGVS:

NC_000006.12:g.110815045G>T
NG_109014.1:g.582G>T
NM_001287215.2:c.-98+230G>T
NM_001300960.2:c.92C>A
NM_001300963.2:c.-115+526C>A
NM_001300964.2:c.-53+763C>A
NM_015076.5:c.92C>AMANE SELECT
NP_001287889.1:p.Thr31Asn
NP_055891.1:p.Thr31Asn
NC_000006.11:g.111136248G>T

Protein change:

T31N; THR31ASN

Links:

OMIM: 614720.0003; dbSNP: rs1783518295

NCBI 1000 Genomes Browser:

rs1783518295

Molecular consequence:

NM_001287215.2:c.-98+230G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001300963.2:c.-115+526C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001300964.2:c.-53+763C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001300960.2:c.92C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015076.5:c.92C>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

functionally_abnormal [Sequence Ontology: SO:0002218]

Observations:

Condition(s)

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

Recent activity

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Mus musculus strain FVB/N fatty acid 2-hydroxylase (Fa2h) mRNA, complete cds
Mus musculus strain FVB/N fatty acid 2-hydroxylase (Fa2h) mRNA, complete cds
gi|56068192|gb|AY660882.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377377	Cipher Gene Genetics Laboratory, Cipher Gene, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 1, 2020)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002518648	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link,
SCV002584925	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

SCV001377377

Cipher Gene Genetics Laboratory, Cipher Gene, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 1, 2020)

de novo

clinical testing

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

SCV002518648

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link,

SCV002584925

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Chinese	de novo	yes	1	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

A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms.

Yang S, Yu W, Chen Q, Wang X.

Cold Spring Harb Mol Case Stud. 2021 Apr 8;7(2). doi:pii: a006082. 10.1101/mcs.a006082. Print 2021 Apr.

PubMed [citation]

PMID:: 33568421
PMCID:: PMC8040737

Details of each submission

From Cipher Gene Genetics Laboratory, Cipher Gene, Inc, SCV001377377.1

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

Description

The de novo variant Thr31Asn in CDK19 was identified through a Trio-WES test in the patient with global developmental delay clinically marked with infantile spasms. Its neighboring amino acid change of Tyr32His was verified to be pathogenic for a early infantile epileptic encephalopathy patient (PubMed: 32330417).

#	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		1	not provided	not provided	not provided

From Mendelics, SCV002518648.1

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

#	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

From OMIM, SCV002584925.1

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

Description

In a 10-month-old boy with developmental and epileptic encephalopathy-87 (DEE87; 618916), Yang et al. (2021) used trio-based whole-exome sequencing to identify a de novo heterozygous c.92C-A transversion (c.92C-A) in exon 1 of the CDK19 gene, resulting in a thr31-to-asn substitution (T31N) at an evolutionarily conserved residue. Molecular modeling showed that the variant occurred at the upper surface of the ligand-binding pocket surrounding the ATP-binding site, suggesting that the variant may disrupt kinase activity. The patient had onset of infantile spasms at 4 months of age.

#	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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