NM_004531.5(MOCS2):c.539_540del (p.Lys180fs) AND Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jan 17, 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:: RCV000006482.12

Allele description [Variation Report for NM_004531.5(MOCS2):c.539_540del (p.Lys180fs)]

NM_004531.5(MOCS2):c.539_540del (p.Lys180fs)

Gene:

MOCS2:molybdenum cofactor synthesis 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q11.2

Genomic location:

Preferred name:

NM_004531.5(MOCS2):c.539_540del (p.Lys180fs)

HGVS:

NC_000005.10:g.53098630_53098631del
NG_008435.2:g.16139_16140del
NM_004531.5:c.539_540delMANE SELECT
NM_176806.4:c.*459_*460del
NP_004522.1:p.Lys180fs
NC_000005.9:g.52394459_52394460del
NC_000005.9:g.52394460_52394461del
NM_004531.3:c.539_540delAA
NM_004531.5:c.539_540delAAMANE SELECT

Protein change:

K180fs

Links:

OMIM: 603708.0001; dbSNP: rs398122797

NCBI 1000 Genomes Browser:

rs398122797

Molecular consequence:

NM_176806.4:c.*459_*460del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_004531.5:c.539_540del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B
Synonyms:: Molybdenum cofactor deficiency, complementation group B; Molybdenum cofactor deficiency B
Identifiers:: MONDO: MONDO:0009644; MedGen: C1854989; Orphanet: 833; OMIM: 252160

Recent activity

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hypothetical protein Np450711_209 [Cyanophage S-RIM14]
hypothetical protein Np450711_209 [Cyanophage S-RIM14]
gi|1063212854|gb|AOO13970.1|

Protein
unnamed protein product [Homo sapiens]
unnamed protein product [Homo sapiens]
gi|732757|emb|CAA29546.1|

Protein
Rattus norvegicus TL0ADA10YK13 mRNA sequence
Rattus norvegicus TL0ADA10YK13 mRNA sequence
gi|298887314|emb|FQ223495.1|

Nucleotide
Facklamia sp. CCUG30090 16S rRNA gene
Facklamia sp. CCUG30090 16S rRNA gene
gi|5701841|emb|Y17820.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026665	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2003)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10053004, 12754701
SCV000245633	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Dec 29, 2014)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10053004, 24033266
SCV002810922	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 17, 2022)	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

SCV000026665

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2003)

germline

literature only

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

SCV000245633

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Dec 29, 2014)

germline

clinical testing

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

SCV002810922

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 17, 2022)

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	1	1	not provided	not provided	not provided	literature only, clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH.

Reiss J, Johnson JL.

Hum Mutat. 2003 Jun;21(6):569-76. Review.

PubMed [citation]

PMID:: 12754701

Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B.

Reiss J, Dorche C, Stallmeyer B, Mendel RR, Cohen N, Zabot MT.

Am J Hum Genet. 1999 Mar;64(3):706-11.

PubMed [citation]

PMID:: 10053004
PMCID:: PMC1377787

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000026665.5

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

Description

In 4 patients with molybdenum cofactor deficiency type B (MOCODB; 252160), Reiss et al. (1999) identified a 2-bp deletion, 726del2, in the MOCS2 gene, removing the last 9 amino acids of the gene product. The mutation was found in homozygous state in 3 patients (1 French, 1 Portuguese, and 1 English) and in compound heterozygous state in a German patient with an E168K missense mutation (603708.0002). This deletion mutation accounted for 50% (7 of 14) of identified alleles.

Reiss and Johnson (2003) reported that the 726delAA frameshift deletion is the most common MOCS2B mutation, having been found on 11 of 28 alleles. They speculated that the prevalence of this mutation in port cities of Portugal, France, the Netherlands, and Germany raises the possibility of distribution by a merchant sailor.

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine - CSER-MedSeq, SCV000245633.1

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

Description

The p.Lys180ArgfsX31 variant in MOCS2 has been reported in 4 individuals with clinical features of molybdenum cofactor deficiency (Reiss 1999). Three of these individuals were homozygous for this variant and one individual was compound heterozygous. This variant has also been identified in 0.01% (5/67564) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs398122797). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 180. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Homozygous or compound heterozygous mutation in the MOCS2 gene have been shown to cause molybdenum cofactor deficiency. In summary, although additional studies are required to fully establish its clinical significance, the p.Lys180ArgfsX31 variant is likely pathogenic.

#	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		1	not provided	1	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002810922.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 15, 2024

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