2-55233917-A-G

Variant names:

• chr2-55233917-A-G
• rs80273115
• NM_002954.6:c.104-202A>G

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.104-202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 625,510 control chromosomes in the GnomAD database, including 6,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1186 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5134 hom.)
• Consequence: RPS27A NM_002954.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.411

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=-0.92).
• BP6: Variant 2-55233917-A-G is Benign according to our data. Variant chr2-55233917-A-G is described in ClinVar as [Benign]. Clinvar id is 1292680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.104-202A>G		intron_variant	Intron 3 of 5	ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.104-202A>G		intron_variant	Intron 3 of 5		NP_001129064.1
RPS27A	NM_001177413.1	c.104-202A>G		intron_variant	Intron 2 of 4		NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.104-202A>G		intron_variant	Intron 3 of 5	1	NM_002954.6	ENSP00000272317.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16580 AN: 152114 Hom.: 1188 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.137 AC: 64949 AN: 473276 Hom.: 5134 Cov.: 3 AF XY: 0.136 AC XY: 34182 AN XY: 251628

Gnomad4 AFR exome AF: 0.0317 AC: 416 AN: 13114

Gnomad4 AMR exome AF: 0.210 AC: 4827 AN: 22994

Gnomad4 ASJ exome AF: 0.138 AC: 2007 AN: 14566

Gnomad4 EAS exome AF: 0.266 AC: 8170 AN: 30688

Gnomad4 SAS exome AF: 0.123 AC: 5967 AN: 48522

Gnomad4 FIN exome AF: 0.0881 AC: 3509 AN: 39820

Gnomad4 NFE exome AF: 0.131 AC: 36133 AN: 275176

Gnomad4 Remaining exome AF: 0.135 AC: 3550 AN: 26386

GnomAD4 genome AF: 0.109 AC: 16562 AN: 152234 Hom.: 1186 Cov.: 32 AF XY: 0.111 AC XY: 8235 AN XY: 74434

Gnomad4 AFR AF: 0.0310 AC: 0.0309688 AN: 0.0309688

Gnomad4 AMR AF: 0.173 AC: 0.172906 AN: 0.172906

Gnomad4 ASJ AF: 0.142 AC: 0.141993 AN: 0.141993

Gnomad4 EAS AF: 0.255 AC: 0.25464 AN: 0.25464

Gnomad4 SAS AF: 0.133 AC: 0.132877 AN: 0.132877

Gnomad4 FIN AF: 0.0867 AC: 0.0866616 AN: 0.0866616

Gnomad4 NFE AF: 0.131 AC: 0.130974 AN: 0.130974

Gnomad4 OTH AF: 0.108 AC: 0.107583 AN: 0.107583

Alfa AF: 0.117 Hom.: 329

Bravo AF: 0.113

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.22
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

Publications

LitVar

Other links and lift over

dbSNP: rs80273115; hg19: chr2-55461053; COSMIC: COSV55054953; COSMIC: COSV55054953;