dbSNP rs199558614: RPS2:p.Pro11Ser (chr16-1964595-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002952.4(RPS2):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,384,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPS2
NM_002952.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.182224).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS2	NM_002952.4 link	c.31C>T	p.Pro11Ser	missense_variant	Exon 2 of 7	ENST00000343262.9	NP_002943.2	P15880

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS2	ENST00000343262.9 link	c.31C>T	p.Pro11Ser	missense_variant	Exon 2 of 7	1	NM_002952.4	ENSP00000341885.4		P15880

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000576

AC:

AN:

173470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

97946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000796

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1384350

Hom.:

Cov.:

AF XY:

0.00000727

AC XY:

AN XY:

687918

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000323

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;T;.;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;T;T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.040

N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.31

T;T;D;T;D

Sift4G

Benign

0.090

T;T;T;T;T

Polyphen

0.0060

B;B;.;.;.

Vest4

0.33

MutPred

0.26

Gain of phosphorylation at P11 (P = 0.0056);Gain of phosphorylation at P11 (P = 0.0056);Gain of phosphorylation at P11 (P = 0.0056);Gain of phosphorylation at P11 (P = 0.0056);Gain of phosphorylation at P11 (P = 0.0056);

MVP

0.92

MPC

0.79

ClinPred

0.37

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.086

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over