rs397518417

Positions:

• chr5-53109714-GGCACAGCGGCACCATCCCGCCTA-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The ENST00000450852.8(MOCS2):​c.-8_15del variant causes a start lost, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOCS2 ENST00000450852.8 start_lost, 5_prime_UTR
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.20

Genes affected

MOCS2 (HGNC:7193): (molybdenum cofactor synthesis 2) Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-53109714-GGCACAGCGGCACCATCCCGCCTA-G is Pathogenic according to our data. Variant chr5-53109714-GGCACAGCGGCACCATCCCGCCTA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 6116.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-53109714-GGCACAGCGGCACCATCCCGCCTA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_004531.5	c.-656_-634del		5_prime_UTR_variant	1/7	ENST00000396954.8	NP_004522.1
MOCS2	NM_176806.4	c.-8_15del		start_lost, 5_prime_UTR_variant	1/7	ENST00000450852.8	NP_789776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS2	ENST00000396954.8	c.-656_-634del		5_prime_UTR_variant	1/7	1	NM_004531.5	ENSP00000380157	P1
MOCS2	ENST00000450852.8	c.-8_15del		start_lost, 5_prime_UTR_variant	1/7	1	NM_176806.4	ENSP00000411022

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	Jul 05, 2023	PVS1, PM2 -
Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 2006	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397518417; hg19: chr5-52405544;