Genetic Variant MOCS2:c.*2158C>T (chr5-53096444-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0710

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
MOCS2	NM_004531.5 link	c.*2158C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000396954.8	NP_004522.1	O96007A0A024QZS1
MOCS2	NM_176806.4 link	c.*2645C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000450852.8	NP_789776.1	O96033

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MOCS2	ENST00000396954 link	c.*2158C>T	3_prime_UTR_variant	Exon 7 of 7	1	NM_004531.5	ENSP00000380157.3	O96007
MOCS2	ENST00000450852 link	c.*2645C>T	3_prime_UTR_variant	Exon 7 of 7	1	NM_176806.4	ENSP00000411022.3	O96033
MOCS2	ENST00000361377 link	c.*2494C>T	3_prime_UTR_variant	Exon 6 of 6	4		ENSP00000355160.4	O96033

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30825

AN:

151976

Hom.:

3686

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.203

AC:

30842

AN:

152094

Hom.:

3694

Cov.:

AF XY:

0.204

AC XY:

15146

AN XY:

74348

show subpopulations

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

LINK: link

Submissions by phenotype

Platelet-type bleeding disorder 9

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over