rs17298242

Variant names:

• chr5-53096444-G-A
• rs17298242
• NM_004531.5:c.*2158C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004531.5(MOCS2):​c.*2158C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,094 control chromosomes in the GnomAD database, including 3,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3694 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOCS2 NM_004531.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0710
• Publications: 3 publications found

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]

MOCS2 Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-53096444-G-A is Benign according to our data. Variant chr5-53096444-G-A is described in ClinVar as Benign. ClinVar VariationId is 903789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004531.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS2	NM_004531.5	MANE Select	c.*2158C>T		3_prime_UTR	Exon 7 of 7	NP_004522.1	O96007
	MOCS2	NM_176806.4	MANE Plus Clinical	c.*2645C>T		3_prime_UTR	Exon 7 of 7	NP_789776.1	O96033

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS2	ENST00000396954.8	TSL:1 MANE Select	c.*2158C>T		3_prime_UTR	Exon 7 of 7	ENSP00000380157.3	O96007
	MOCS2	ENST00000450852.8	TSL:1 MANE Plus Clinical	c.*2645C>T		3_prime_UTR	Exon 7 of 7	ENSP00000411022.3	O96033
	MOCS2	ENST00000855414.1		c.*2158C>T		3_prime_UTR	Exon 6 of 6	ENSP00000525473.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30825 AN: 151976 Hom.: 3686 Cov.: 33

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.209

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.203 AC: 30842 AN: 152094 Hom.: 3694 Cov.: 33 AF XY: 0.204 AC XY: 15146 AN XY: 74348

African (AFR) AF: 0.0746 AC: 3096 AN: 41514

American (AMR) AF: 0.237 AC: 3616 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.0839 AC: 434 AN: 5170

South Asian (SAS) AF: 0.274 AC: 1320 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2736 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.264 AC: 17968 AN: 67978

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.221 Hom.: 654

Bravo AF: 0.191

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Platelet-type bleeding disorder 9 (1)
-	-	1	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.071
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17298242; hg19: chr5-52392274; COSMIC: COSV56857908; COSMIC: COSV56857908;