chr5-53096444-G-A

Position:

• chr5-53096444-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_004531.5	c.*2158C>T		3_prime_UTR_variant	7/7	ENST00000396954.8	NP_004522.1
MOCS2	NM_176806.4	c.*2645C>T		3_prime_UTR_variant	7/7	ENST00000450852.8	NP_789776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS2	ENST00000396954.8	c.*2158C>T		3_prime_UTR_variant	7/7	1	NM_004531.5	ENSP00000380157	P1
MOCS2	ENST00000450852.8	c.*2645C>T		3_prime_UTR_variant	7/7	1	NM_176806.4	ENSP00000411022
MOCS2	ENST00000361377.8	c.*2494C>T		3_prime_UTR_variant	6/6	4		ENSP00000355160

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.207

Alfa AF: 0.221 Hom.: 654

Bravo AF: 0.191

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Platelet-type bleeding disorder 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

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