16-1964488-T-G

Variant names:

• chr16-1964488-T-G
• rs78924165
• NM_002952.4:c.138A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002952.4(RPS2):​c.138A>C​(p.Arg46Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,118 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. Synonymous variant affecting the same amino acid position (i.e. R46R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPS2 NM_002952.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 2 publications found

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]

SNHG9 (HGNC:33102): (small nucleolar RNA host gene 9)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.56 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS2	NM_002952.4	MANE Select	c.138A>C	p.Arg46Arg	synonymous	Exon 2 of 7	NP_002943.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS2	ENST00000343262.9	TSL:1 MANE Select	c.138A>C	p.Arg46Arg	synonymous	Exon 2 of 7	ENSP00000341885.4	P15880
	RPS2	ENST00000527109.5	TSL:1	n.143A>C		non_coding_transcript_exon	Exon 1 of 5
	RPS2	ENST00000527826.1	TSL:1	n.318A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455118 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723758

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4578

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109938

Other (OTH) AF: 0.00 AC: 0 AN: 59950

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.8
DANN	Benign	0.86
PhyloP100		-0.56
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs78924165; hg19: chr16-2014489;