rs116840806

Variant names:

• chr10-78035352-AAC-TACGGATAG
• rs116840806
• NM_033022.4:c.4_6delAACinsTACGGATAG

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_033022.4(RPS24):​c.4_6delAACinsTACGGATAG​(p.Asn2delinsTyrGlyTer) variant causes a stop gained, missense, conservative inframe insertion, splice region 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. N2N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS24 NM_033022.4 stop_gained, missense, conservative_inframe_insertion, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.99
• Publications: 1 publications found

Genes affected

RPS24 (HGNC:10411): (ribosomal protein S24) 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 S24E family of ribosomal proteins. It is located in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. 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. [provided by RefSeq, Nov 2008]

RPS24 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-78035352-AAC-TACGGATAG is Pathogenic according to our data. Variant chr10-78035352-AAC-TACGGATAG is described in ClinVar as Pathogenic. ClinVar VariationId is 7247.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS24	NM_033022.4	c.4_6delAACinsTACGGATAG	p.Asn2delinsTyrGlyTer	stop_gained, missense_variant, conservative_inframe_insertion, splice_region_variant	Exon 2 of 6	ENST00000372360.9	NP_148982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS24	ENST00000372360.9	c.4_6delAACinsTACGGATAG	p.Asn2delinsTyrGlyTer	stop_gained, missense_variant, conservative_inframe_insertion, splice_region_variant	Exon 2 of 6	1	NM_033022.4	ENSP00000361435.4
RPS24	ENST00000435275.5	c.4_6delAACinsTACGGATAG	p.Asn2delinsTyrGlyTer	stop_gained, missense_variant, conservative_inframe_insertion, splice_region_variant	Exon 2 of 6	2		ENSP00000415549.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Diamond-Blackfan anemia 3 Pathogenic:1

Dec 01, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116840806; hg19: chr10-79795110;