Variant chr16-1964528-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002952.4(RPS2):c.98T>G(p.Ile33Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPS2
NM_002952.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

RPS2 (HGNC:10404): (ribosomal protein S2) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S5P family of ribosomal proteins. It is located in the cytoplasm. This gene shares sequence similarity with mouse LLRep3. It is co-transcribed with the small nucleolar RNA gene U64, which is located in its third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14448851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS2	NM_002952.4 linkuse as main transcript	c.98T>G	p.Ile33Ser	missense_variant	2/7	ENST00000343262.9	NP_002943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS2	ENST00000343262.9 linkuse as main transcript	c.98T>G	p.Ile33Ser	missense_variant	2/7	1	NM_002952.4	ENSP00000341885	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.98T>G (p.I33S) alteration is located in exon 2 (coding exon 1) of the RPS2 gene. This alteration results from a T to G substitution at nucleotide position 98, causing the isoleucine (I) at amino acid position 33 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.029

T;T;.;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.63

N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.082

T;T;D;T;T

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.0030

B;B;.;.;.

Vest4

0.31

MutPred

0.33

Gain of phosphorylation at I33 (P = 3e-04);Gain of phosphorylation at I33 (P = 3e-04);Gain of phosphorylation at I33 (P = 3e-04);Gain of phosphorylation at I33 (P = 3e-04);Gain of phosphorylation at I33 (P = 3e-04);

MVP

0.75

MPC

1.1

ClinPred

0.38

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over