16-1964488-T-C

Position:

• chr16-1964488-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002952.4(RPS2):​c.138A>G​(p.Arg46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,607,308 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (137 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (114 hom.)
• Consequence: RPS2 NM_002952.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.560

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 16-1964488-T-C is Benign according to our data. Variant chr16-1964488-T-C is described in ClinVar as [Benign]. Clinvar id is 768738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS2	NM_002952.4	c.138A>G	p.Arg46=	synonymous_variant	2/7	ENST00000343262.9	NP_002943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS2	ENST00000343262.9	c.138A>G	p.Arg46=	synonymous_variant	2/7	1	NM_002952.4	ENSP00000341885	P1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3262 AN: 152084 Hom.: 136 Cov.: 34

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00507 AC: 1187 AN: 234104 Hom.: 45 AF XY: 0.00390 AC XY: 503 AN XY: 129132

Gnomad AFR exome AF: 0.0790

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.000209

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.00211

GnomAD4 exome AF: 0.00216 AC: 3143 AN: 1455106 Hom.: 114 Cov.: 33 AF XY: 0.00181 AC XY: 1311 AN XY: 723754

Gnomad4 AFR exome AF: 0.0774

Gnomad4 AMR exome AF: 0.00358

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000784

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.0215 AC: 3271 AN: 152202 Hom.: 137 Cov.: 34 AF XY: 0.0205 AC XY: 1523 AN XY: 74416

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00178 Hom.: 1

Bravo AF: 0.0247

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.1
DANN	Benign	0.80

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: rs78924165; hg19: chr16-2014489;