NM_033661.4(WDR4):c.[491A>C];[940dup] AND Microcephalic primordial dwarfism

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2017
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:: RCV000625529.2

Allele description [Variation Report for NM_033661.4(WDR4):c.[491A>C];[940dup]]

NM_018669.6(WDR4):c.491A>C (p.Asp164Ala)

Gene:

WDR4:WD repeat domain 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_018669.6(WDR4):c.491A>C (p.Asp164Ala)

HGVS:

NC_000021.9:g.42862357T>G
NM_001260474.2:c.491A>C
NM_001260475.2:c.53A>C
NM_001260476.2:c.53A>C
NM_001260477.2:c.53A>C
NM_018669.6:c.491A>CMANE SELECT
NM_033661.5:c.491A>C
NP_001247403.1:p.Asp164Ala
NP_001247404.1:p.Asp18Ala
NP_001247405.1:p.Asp18Ala
NP_001247406.1:p.Asp18Ala
NP_061139.2:p.Asp164Ala
NP_387510.1:p.Asp164Ala
NP_387510.1:p.Asp164Ala
NC_000021.8:g.44282467T>G
NM_033661.4:c.491A>C
NR_048535.1:n.471A>C
p.D164A

Protein change:

D164A; ASP164ALA

Links:

OMIM: 605924.0004; dbSNP: rs1555976610

NCBI 1000 Genomes Browser:

rs1555976610

Molecular consequence:

NM_001260474.2:c.491A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001260475.2:c.53A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001260476.2:c.53A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001260477.2:c.53A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_018669.6:c.491A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033661.5:c.491A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_048535.1:n.471A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

NM_018669.6(WDR4):c.940dup (p.Leu314fs)

Gene:

WDR4:WD repeat domain 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_018669.6(WDR4):c.940dup (p.Leu314fs)

HGVS:

NC_000021.9:g.42853609dup
NM_001260474.2:c.937dup
NM_001260475.2:c.502dup
NM_001260476.2:c.502dup
NM_001260477.2:c.502dup
NM_018669.6:c.940dupMANE SELECT
NM_033661.5:c.940dup
NP_001247403.1:p.Leu313fs
NP_001247404.1:p.Leu168fs
NP_001247405.1:p.Leu168fs
NP_001247406.1:p.Leu168fs
NP_061139.2:p.Leu314fs
NP_387510.1:p.Leu314fs
NC_000021.8:g.44273719dup
NM_033661.4:c.940dupC
NR_048535.1:n.920dup

Protein change:

L168fs

Links:

OMIM: 605924.0005; dbSNP: rs776760122

NCBI 1000 Genomes Browser:

rs776760122

Molecular consequence:

NM_001260474.2:c.937dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001260475.2:c.502dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001260476.2:c.502dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001260477.2:c.502dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018669.6:c.940dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033661.5:c.940dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_048535.1:n.920dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Microcephalic primordial dwarfism
Identifiers:: MedGen: CN437676; Orphanet: 324761

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RRM1 ribonucleotide reductase catalytic subunit M1 [Homo sapiens]
RRM1 ribonucleotide reductase catalytic subunit M1 [Homo sapiens]
Gene ID:6240

Gene
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Gene
Crassostrea angulata
Crassostrea angulata
Crassostrea angulata Raw sequence reads

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Gene Links for GEO Profiles (Select 106876553) (2)
Gene
Myotis atacamensis mitochondrion, complete genome
Myotis atacamensis mitochondrion, complete genome
gi|1270115040|gb|MF143493.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000598652	The Translational Medicine Center of Children Development and Disease, Fudan University	criteria provided, single submitter (Submitter's publication)	Uncertain significance (Sep 1, 2017)	inherited	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26416026, 28617965, 29597095

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000598652

The Translational Medicine Center of Children Development and Disease, Fudan University

criteria provided, single submitter

(Submitter's publication)

Uncertain significance
(Sep 1, 2017)

inherited

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
Chinese Han population	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

Shaheen R, Abdel-Salam GM, Guy MP, Alomar R, Abdel-Hamid MS, Afifi HH, Ismail SI, Emam BA, Phizicky EM, Alkuraya FS.

Genome Biol. 2015 Sep 28;16:210. doi: 10.1186/s13059-015-0779-x.

PubMed [citation]

PMID:: 26416026
PMCID:: PMC4587777

Further delineation of the phenotype caused by biallelic variants in the WDR4 gene.

Trimouille A, Lasseaux E, Barat P, Deiller C, Drunat S, Rooryck C, Arveiler B, Lacombe D.

Clin Genet. 2018 Feb;93(2):374-377. doi: 10.1111/cge.13074. Epub 2017 Sep 29.

PubMed [citation]

PMID:: 28617965

See all PubMed Citations (3)

Details of each submission

From The Translational Medicine Center of Children Development and Disease, Fudan University, SCV000598652.1

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

Description

A term baby was born to a non-consanguineous couple by cesarean section. His birth weight was 2650g and has no condition of intrauterine growth retardation. Head circumference is not recorded but mentioned to be smaller than normal range. He did not require the age-appropriate developmental milestones. He was able to walk at 2-year-old without spasticity or abnormal gait. He presents persistent speech development delay as saying single simple words at 3-year-old and unable to say a complete sentence at 6-year-old. He is 110 cm at 6-year-old which is slightly lower than normal range (111.2â€”121.0cm). Family history of similar condition is negative. The scores of Developmental Screen Test (DST) are low: Developmental Quotient (DQ) is less than 50 and Mental Index (MI) is less than 49. Scores of DQ and MI both less than 70 means abnormal development degree. The results of tandem mass, thyroid function test, cranial magnetic resonance imaging (MRI), electroencephalograph are normal. The diagnosis of this patient in clinical is global developmental delay.

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

Last Updated: Jan 26, 2024

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