2-46308468-G-GGGGC

Variant names:

• chr2-46308468-G-GGGGC
• rs1558582262
• NM_001430.5:c.26+10532_26+10535dupGGGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001430.5(EPAS1):​c.26+10532_26+10535dupGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

Genes affected

EPAS1 (HGNC:3374): (endothelial PAS domain protein 1) This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.26+10532_26+10535dupGGGC		intron_variant	Intron 1 of 15	ENST00000263734.5	NP_001421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.26+10531_26+10532insGGGC		intron_variant	Intron 1 of 15	1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.26+10531_26+10532insGGGC		intron_variant	Intron 2 of 6	3		ENSP00000406137.1
EPAS1	ENST00000460015.1	n.432+14370_432+14371insGGGC		intron_variant	Intron 1 of 1	4
EPAS1	ENST00000467888.5	n.174+10531_174+10532insGGGC		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 138686 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000315

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000144 AC: 2 AN: 138686 Hom.: 0 Cov.: 27 AF XY: 0.0000149 AC XY: 1 AN XY: 66962

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000315

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs1558582262; hg19: chr2-46535607;