rs1555716041

Positions:

• chr19-11378205-AGAGCTGG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_000121.4(EPOR):​c.1299_1305delCCAGCTC​(p.Gln434fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPOR NM_000121.4 frameshift
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 2.38

Genes affected

EPOR (HGNC:3416): (erythropoietin receptor) This gene encodes the erythropoietin receptor which is a member of the cytokine receptor family. Upon erythropoietin binding, this receptor activates Jak2 tyrosine kinase which activates different intracellular pathways including: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. The stimulated erythropoietin receptor appears to have a role in erythroid cell survival. Defects in the erythropoietin receptor may produce erythroleukemia and familial erythrocytosis. Dysregulation of this gene may affect the growth of certain tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

EPOR (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPOR	NM_000121.4	c.1299_1305delCCAGCTC	p.Gln434fs	frameshift_variant	8/8	ENST00000222139.11	NP_000112.1
EPOR	NR_033663.2	n.1656_1662delCCAGCTC		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPOR	ENST00000222139.11	c.1299_1305delCCAGCTC	p.Gln434fs	frameshift_variant	8/8	1	NM_000121.4	ENSP00000222139.5

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: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Primary familial polycythemia due to EPO receptor mutation Other:1

Affects, no assertion criteria provided

literature only

OMIM

Sep 01, 1997

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555716041; hg19: chr19-11488881;