Genetic Variant NM_002952.4:c.772G>A (chr16-1962208-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002952.4(RPS2):c.772G>A(p.Glu258Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPS2
NM_002952.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

Publications

0 publications found

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:

NDUFB10 (HGNC:7696): (NADH:ubiquinone oxidoreductase subunit B10) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 35. [provided by Alliance of Genome Resources, Apr 2022]

NDUFB10 links:

SNORA10 (HGNC:32598): (small nucleolar RNA, H/ACA box 10)

SNORA10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002952.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS2	NM_002952.4	MANE Select	c.772G>A	p.Glu258Lys	missense	Exon 7 of 7	NP_002943.2
NDUFB10	NM_004548.3	MANE Select	c.*302C>T		downstream_gene	N/A	NP_004539.1	A8K761
SNORA10	NR_002327.1		n.*126G>A		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS2	ENST00000343262.9	TSL:1 MANE Select	c.772G>A	p.Glu258Lys	missense	Exon 7 of 7	ENSP00000341885.4	P15880
RPS2	ENST00000527109.5	TSL:1	n.883G>A		non_coding_transcript_exon	Exon 5 of 5
RPS2	ENST00000527871.5	TSL:1	n.1096G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1455668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110812

Other (OTH)

AF:

0.00

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

-0.039

MutationAssessor

Uncertain

2.1

PhyloP100

7.8

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

REVEL

Benign

0.22

Sift

Benign

0.065

Sift4G

Benign

0.10

Polyphen

0.95

Vest4

0.81

MutPred

0.48

Gain of methylation at E258 (P = 0.0263)

MVP

0.53

MPC

1.4

ClinPred

0.95

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.68

gMVP

0.89

Mutation Taster

=42/58

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over