16-1964604-C-T

Variant names:

• chr16-1964604-C-T
• rs772256506
• NM_002952.4:c.22G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002952.4(RPS2):​c.22G>A​(p.Ala8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000219 in 1,367,816 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: 0.0000022 (0 hom.)
• Consequence: RPS2 NM_002952.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3402925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS2	NM_002952.4	c.22G>A	p.Ala8Thr	missense_variant	Exon 2 of 7	ENST00000343262.9	NP_002943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS2	ENST00000343262.9	c.22G>A	p.Ala8Thr	missense_variant	Exon 2 of 7	1	NM_002952.4	ENSP00000341885.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367816 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 679052

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: 0.00000281

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ExAC AF: 0.00000864 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T;T;T;T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.7	L;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.35	N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.044	D;T;D;T;T
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.81	P;P;.;.;.
Vest4		0.59
MutPred		0.14		Gain of glycosylation at A8 (P = 0.0034);Gain of glycosylation at A8 (P = 0.0034);Gain of glycosylation at A8 (P = 0.0034);Gain of glycosylation at A8 (P = 0.0034);Gain of glycosylation at A8 (P = 0.0034);
MVP		0.90
MPC		0.76
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.17
gMVP		0.16

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

Other links and lift over

dbSNP: rs772256506; hg19: chr16-2014605;