Genetic Variant RIOK2:p.Ala302Val (chr5-97167959-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018343.3(RIOK2):c.905C>T(p.Ala302Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RIOK2
NM_018343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80

Publications

0 publications found

Variant links:

Genes affected

RIOK2 (HGNC:18999): (RIO kinase 2) Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

RIOK2 links:

LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

LIX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3533529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3 link	c.905C>T	p.Ala302Val	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2	Q9BVS4-1
RIOK2	NM_001159749.2 link	c.905C>T	p.Ala302Val	missense_variant	Exon 8 of 8		NP_001153221.1	Q9BVS4-2
RIOK2	XM_017009628.2 link	c.344C>T	p.Ala115Val	missense_variant	Exon 6 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIOK2	ENST00000283109.8 link	c.905C>T	p.Ala302Val	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3	Q9BVS4-1
RIOK2	ENST00000508447.1 link	c.905C>T	p.Ala302Val	missense_variant	Exon 8 of 8	1		ENSP00000420932.1	Q9BVS4-2
LIX1-AS1	ENST00000504578.2 link	n.574-15049G>A		intron_variant	Intron 3 of 6	5
RIOK2	ENST00000511012.1 link	c.-242C>T		upstream_gene_variant		2		ENSP00000422772.1	H0Y919

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722498

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111438

Other (OTH)

AF:

0.00

AC:

AN:

60290

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.905C>T (p.A302V) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a C to T substitution at nucleotide position 905, causing the alanine (A) at amino acid position 302 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.0062

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

6.8

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.17

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

0.96

D;.

Vest4

0.39

MutPred

0.39

Loss of sheet (P = 0.003);Loss of sheet (P = 0.003);

MVP

0.83

MPC

0.34

ClinPred

0.97

GERP RS

5.7

PromoterAI

-0.048

Neutral

(source)

Varity_R

0.70

gMVP

0.67

Mutation Taster

=25/75

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over