5-97167944-T-C

Variant names:

• chr5-97167944-T-C
• NM_018343.3:c.920A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018343.3(RIOK2):​c.920A>G​(p.Lys307Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93
• Publications: 0 publications found

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]

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

ACMG classification

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=0.2955643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.920A>G	p.Lys307Arg	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.920A>G	p.Lys307Arg	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.359A>G	p.Lys120Arg	missense_variant	Exon 6 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.920A>G	p.Lys307Arg	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3
RIOK2	ENST00000508447.1	c.920A>G	p.Lys307Arg	missense_variant	Exon 8 of 8	1		ENSP00000420932.1
LIX1-AS1	ENST00000504578.2	n.574-15064T>C		intron_variant	Intron 3 of 6	5
RIOK2	ENST00000511012.1	c.-227A>G		upstream_gene_variant		2		ENSP00000422772.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.920A>G (p.K307R) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a A to G substitution at nucleotide position 920, causing the lysine (K) at amino acid position 307 to be replaced by an arginine (R). 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	Benign	0.076
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M
PhyloP100		7.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.21
Sift	Benign	0.079	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.056	B;.
Vest4		0.41
MutPred		0.40		Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);
MVP		0.43
MPC		0.12
ClinPred		0.87	D
GERP RS		5.7
PromoterAI		-0.041	Neutral
Varity_R		0.60
gMVP		0.43
Mutation Taster		=8/92	disease causing

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

Other links and lift over

hg19: chr5-96503648;