NM_001136193.2(FASTKD2):c.868C>T (p.Arg290Ter) AND Combined oxidative phosphorylation deficiency 44

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 20, 2023
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:: RCV001090022.4

Allele description [Variation Report for NM_001136193.2(FASTKD2):c.868C>T (p.Arg290Ter)]

NM_001136193.2(FASTKD2):c.868C>T (p.Arg290Ter)

Genes:

LOC126806484:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:207634423-207635622 [Gene]
FASTKD2:FAST kinase domains 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.3

Genomic location:

Preferred name:

NM_001136193.2(FASTKD2):c.868C>T (p.Arg290Ter)

HGVS:

NC_000002.12:g.206770181C>T
NG_008984.1:g.9794C>T
NM_001136193.2:c.868C>TMANE SELECT
NM_001136194.2:c.868C>T
NM_014929.4:c.868C>T
NP_001129665.1:p.Arg290Ter
NP_001129666.1:p.Arg290Ter
NP_055744.2:p.Arg290Ter
NP_055744.2:p.Arg290Ter
NC_000002.11:g.207634905C>T
NM_014929.3:c.868C>T

Protein change:

R290*; ARG290TER

Links:

OMIM: 612322.0004; dbSNP: rs778120270

NCBI 1000 Genomes Browser:

rs778120270

Molecular consequence:

NM_001136193.2:c.868C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001136194.2:c.868C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014929.4:c.868C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Combined oxidative phosphorylation deficiency 44
Identifiers:: MONDO: MONDO:0030020; MedGen: C5394293; OMIM: 618855

Recent activity

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C-type LECtin [Caenorhabditis elegans]
C-type LECtin [Caenorhabditis elegans]
gi|17541614|ref|NP_502826.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001245430	OMIM	no assertion criteria provided	Pathogenic (May 1, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004235788	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 20, 2023)	germline	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

SCV001245430

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2020)

germline

literature only

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

SCV004235788

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 20, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency.

Wei X, Du M, Li D, Wen S, Xie J, Li Y, Chen A, Zhang K, Xu P, Jia M, Wen C, Zhou H, Lyu J, Yang Y, Fang H.

Hum Mutat. 2020 May;41(5):961-972. doi: 10.1002/humu.23985. Epub 2020 Jan 30.

PubMed [citation]

PMID:: 31944455

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

Details of each submission

From OMIM, SCV001245430.1

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

Description

In a Chinese patient (patient 2) with combined oxidative phosphorylation deficiency-44 (COXPD44; 618855), Wei et al. (2020) identified a homozygous c.868C-T transition (c.868C-T, NM_014929.3) in the FASTKD2 gene, resulting in an arg290-to-ter (R290X) substitution. An unrelated Chinese patient with the disorder (patient 3) was found to be compound heterozygous for R290X and a 1-bp deletion (c.1859delT; 612322.0005), resulting in a frameshift and premature termination (Ser621LeufsTer14). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The frameshift mutation was not found in the gnomAD database, whereas R290X was present at a low frequency (3.2 x 10(-5)) in only heterozygous state (1 in 30,950 alleles). Western blot analysis of lymphocytes derived from patient 2 showed undetectable levels of the FASTKD2 protein.

#	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 Revvity Omics, Revvity, SCV004235788.1

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

#	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

Last Updated: May 19, 2024

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