NM_015721.3(GEMIN4):c.2452T>C (p.Trp818Arg) AND Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 3, 2020
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:: RCV000590998.4

Allele description [Variation Report for NM_015721.3(GEMIN4):c.2452T>C (p.Trp818Arg)]

NM_015721.3(GEMIN4):c.2452T>C (p.Trp818Arg)

Gene:

GEMIN4:gem nuclear organelle associated protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_015721.3(GEMIN4):c.2452T>C (p.Trp818Arg)

HGVS:

NC_000017.11:g.745591A>G
NG_046938.1:g.12282T>C
NM_015721.3:c.2452T>CMANE SELECT
NP_056536.2:p.Trp818Arg
NC_000017.10:g.648831A>G
NM_015721.2:c.2452T>C

Protein change:

W818R; TRP818ARG

Links:

OMIM: 606969.0001; dbSNP: rs730882219

NCBI 1000 Genomes Browser:

rs730882219

Molecular consequence:

NM_015721.3:c.2452T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities
Identifiers:: MONDO: MONDO:0060664; MedGen: C4693567; OMIM: 617913

Recent activity

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zinc finger protein 793 isoform X1 [Homo sapiens]
zinc finger protein 793 isoform X1 [Homo sapiens]
gi|2462565360|ref|XP_054176968.1|

Protein
cytochrome oxidase subunit I, partial (mitochondrion) [Atys semistriata]
cytochrome oxidase subunit I, partial (mitochondrion) [Atys semistriata]
gi|1798058070|gb|QHI07421.1|

Protein
ND4L [Clupea pallasii]
ND4L [Clupea pallasii]
Gene ID:5228464

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000700207	OMIM	no assertion criteria provided	Pathogenic (Jan 13, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 25558065, 27878435
SCV001520167	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 3, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000700207

OMIM

no assertion criteria provided

Pathogenic
(Jan 13, 2015)

germline

literature only

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

SCV001520167

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 3, 2020)

unknown

clinical testing

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

Alazami AM, Patel N, Shamseldin HE, Anazi S, Al-Dosari MS, Alzahrani F, Hijazi H, Alshammari M, Aldahmesh MA, Salih MA, Faqeih E, Alhashem A, Bashiri FA, Al-Owain M, Kentab AY, Sogaty S, Al Tala S, Temsah MH, Tulbah M, Aljelaify RF, Alshahwan SA, Seidahmed MZ, et al.

Cell Rep. 2015 Jan 13;10(2):148-61. doi: 10.1016/j.celrep.2014.12.015. Epub 2014 Dec 31.

PubMed [citation]

PMID:: 25558065

Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.

Patel N, Anand D, Monies D, Maddirevula S, Khan AO, Algoufi T, Alowain M, Faqeih E, Alshammari M, Qudair A, Alsharif H, Aljubran F, Alsaif HS, Ibrahim N, Abdulwahab FM, Hashem M, Alsedairy H, Aldahmesh MA, Lachke SA, Alkuraya FS.

Hum Genet. 2017 Feb;136(2):205-225. doi: 10.1007/s00439-016-1747-6. Epub 2016 Nov 22.

PubMed [citation]

PMID:: 27878435
PMCID:: PMC5783298

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000700207.3

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

Description

In 5 children from 3 unrelated consanguineous families (08DG00485, 10DG0703, and 13DG1542) with neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (NEDMCR; 617913), Alazami et al. (2015) identified a homozygous c.2452T-C transition (c.2452T-C, NM_015721) in the GEMIN4 gene, resulting in a trp818-to-arg (W818R) substitution. The mutation, which was found by whole-exome sequencing, segregated with the disorder in each family. Functional studies of the variant and studies of patient cells were not performed.

In a patient (11DG2480) with NEDMCR, Patel et al. (2017) identified homozygosity for the W818R mutation in the GEMIN4 gene.

#	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

From Baylor Genetics, SCV001520167.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Aug 4, 2024

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