rs786203998
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_001029.5(RPS26):c.4-2A>T variant causes a splice acceptor change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
RPS26
NM_001029.5 splice_acceptor
NM_001029.5 splice_acceptor
Scores
2
2
3
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 5.51
Genes affected
RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 10, offset of -19, new splice context is: ttgcgccgttttcctaacAGttt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 12-56042423-A-T is Pathogenic according to our data. Variant chr12-56042423-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 187850.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-56042423-A-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS26 | NM_001029.5 | c.4-2A>T | splice_acceptor_variant | ENST00000646449.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS26 | ENST00000646449.2 | c.4-2A>T | splice_acceptor_variant | NM_001029.5 | P1 | ||||
RPS26 | ENST00000356464.10 | c.4-2A>T | splice_acceptor_variant | 1 | P1 | ||||
RPS26 | ENST00000552361.1 | c.4-2A>T | splice_acceptor_variant | 5 | P1 | ||||
RPS26 | ENST00000548590.1 | n.31-2A>T | splice_acceptor_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2014 | - - |
Diamond-Blackfan anemia 15 with mandibulofacial dysostosis Pathogenic:1
Pathogenic, criteria provided, single submitter | research | University of Washington Center for Mendelian Genomics, University of Washington | May 19, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 8
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at