rs397518451

Positions:

• chr17-8382189-TTC-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000987.5(RPL26):​c.120_121delGA​(p.Lys41fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL26 NM_000987.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.93

Genes affected

RPL26 (HGNC:10327): (ribosomal protein L26) 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 60S subunit. The protein belongs to the L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ENSG00000263809 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-8382189-TTC-T is Pathogenic according to our data. Variant chr17-8382189-TTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 39740.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-8382189-TTC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL26	NM_000987.5	c.120_121delGA	p.Lys41fs	frameshift_variant	2/4	ENST00000648839.1	NP_000978.1
RPL26	NM_001315530.2	c.120_121delGA	p.Lys41fs	frameshift_variant	2/4		NP_001302459.1
RPL26	NM_001315531.2	c.120_121delGA	p.Lys41fs	frameshift_variant	2/4		NP_001302460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL26	ENST00000648839.1	c.120_121delGA	p.Lys41fs	frameshift_variant	2/4		NM_000987.5	ENSP00000498177.1
ENSG00000263809	ENST00000582471.1	n.120_121delGA		non_coding_transcript_exon_variant	2/6	5		ENSP00000463847.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Diamond-Blackfan anemia 11 Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	Jan 01, 2023	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jul 01, 2012	- -

Computational scores

Source: dbNSFP v4.3

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: rs397518451; hg19: chr17-8285507;