11-810296-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_001004.4(RPLP2):c.62A>G(p.Lys21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,457,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPLP2
NM_001004.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

RPLP2 (HGNC:10377): (ribosomal protein lateral stalk subunit P2) 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 phosphoprotein that is a component of the 60S subunit. The protein, which is a functional equivalent of the E. coli L7/L12 ribosomal protein, belongs to the L12P family of ribosomal proteins. It plays an important role in the elongation step of protein synthesis. Unlike most ribosomal proteins, which are basic, the encoded protein is acidic. Its C-terminal end is nearly identical to the C-terminal ends of the ribosomal phosphoproteins P0 and P1. The P2 protein can interact with P0 and P1 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. 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]

RPLP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM1

In a modified_residue N6-acetyllysine; alternate (size 0) in uniprot entity RLA2_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.2660879).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP2	NM_001004.4 link	c.62A>G	p.Lys21Arg	missense_variant	Exon 2 of 5	ENST00000321153.9	NP_000995.1	P05387A0A024RCA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP2	ENST00000321153.9 link	c.62A>G	p.Lys21Arg	missense_variant	Exon 2 of 5	1	NM_001004.4	ENSP00000322419.4		P05387

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245656

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1457008

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724812

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

32986

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44482

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26048

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39236

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85640

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52432

Gnomad4 NFE exome

AF:

0.0000108

AC:

AN:

1110512

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

60200

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 22, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.62A>G (p.K21R) alteration is located in exon 2 (coding exon 1) of the RPLP2 gene. This alteration results from a A to G substitution at nucleotide position 62, causing the lysine (K) at amino acid position 21 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

0.14

BayesDel_addAF

Benign

0.0017

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

-0.092

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.24

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.38

B;B

Vest4

0.34

MutPred

0.39

Loss of ubiquitination at K21 (P = 0.0381);Loss of ubiquitination at K21 (P = 0.0381);

MVP

0.42

MPC

0.41

ClinPred

0.71

GERP RS

4.3

Varity_R

0.13

gMVP

0.43

Mutation Taster

=75/25

polymorphism

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over