2-55234687-T-A

Variant names:

• chr2-55234687-T-A
• rs2576722
• NM_002954.6:c.190-144T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002954.6(RPS27A):​c.190-144T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 878,656 control chromosomes in the GnomAD database, including 297,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52885 hom., cov: 32)
  • Exomes 𝑓: 0.82 (244761 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372
• Publications: 3 publications found

Genes affected

RPS27A (HGNC:10417): (ribosomal protein S27a) Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.[provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-55234687-T-A is Benign according to our data. Variant chr2-55234687-T-A is described in ClinVar as Benign. ClinVar VariationId is 1292677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002954.6. 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
	RPS27A	NM_002954.6	MANE Select	c.190-144T>A		intron	N/A	NP_002945.1	B2RDW1
	RPS27A	NM_001135592.2		c.190-144T>A		intron	N/A	NP_001129064.1	B2RDW1
	RPS27A	NM_001177413.1		c.190-144T>A		intron	N/A	NP_001170884.1	B2RDW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27A	ENST00000272317.11	TSL:1 MANE Select	c.190-144T>A		intron	N/A	ENSP00000272317.6	P62979
	RPS27A	ENST00000404735.1	TSL:1	c.190-144T>A		intron	N/A	ENSP00000385659.1	P62979
	RPS27A	ENST00000859841.1		c.190-144T>A		intron	N/A	ENSP00000529900.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126637 AN: 152100 Hom.: 52852 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.827

GnomAD4 exome AF: 0.819 AC: 595069 AN: 726438 Hom.: 244761 Cov.: 9 AF XY: 0.817 AC XY: 310609 AN XY: 380134

African (AFR) AF: 0.834 AC: 15403 AN: 18466

American (AMR) AF: 0.764 AC: 25007 AN: 32748

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 15020 AN: 20250

East Asian (EAS) AF: 0.687 AC: 22440 AN: 32686

South Asian (SAS) AF: 0.754 AC: 48551 AN: 64408

European-Finnish (FIN) AF: 0.885 AC: 32802 AN: 37048

Middle Eastern (MID) AF: 0.772 AC: 2093 AN: 2712

European-Non Finnish (NFE) AF: 0.839 AC: 404694 AN: 482426

Other (OTH) AF: 0.814 AC: 29059 AN: 35694

GnomAD4 genome AF: 0.833 AC: 126725 AN: 152218 Hom.: 52885 Cov.: 32 AF XY: 0.831 AC XY: 61828 AN XY: 74428

African (AFR) AF: 0.843 AC: 34990 AN: 41502

American (AMR) AF: 0.808 AC: 12358 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3625 AN: 5180

South Asian (SAS) AF: 0.729 AC: 3522 AN: 4828

European-Finnish (FIN) AF: 0.891 AC: 9457 AN: 10608

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57447 AN: 68020

Other (OTH) AF: 0.829 AC: 1754 AN: 2116

Alfa AF: 0.821 Hom.: 2618

Bravo AF: 0.827

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs2576722; hg19: chr2-55461823;