2-46356142-C-CTCT

Variant names:

• chr2-46356142-C-CTCT
• rs35508970
• NM_001430.5:c.218-9_218-8insTCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001430.5(EPAS1):​c.218-9_218-8insTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 NM_001430.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.218-9_218-8insTCT		splice_region_variant, intron_variant	Intron 2 of 15	ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-9_257-8insTCT		splice_region_variant, intron_variant	Intron 2 of 15		XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.218-9_218-8insTCT		splice_region_variant, intron_variant	Intron 2 of 15	1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.218-9_218-8insTCT		splice_region_variant, intron_variant	Intron 3 of 6	3		ENSP00000406137.1
EPAS1	ENST00000463191.1	n.28_29insTCT		non_coding_transcript_exon_variant	Exon 1 of 4	2
EPAS1	ENST00000475822.1	n.409-9_409-8insTCT		splice_region_variant, intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1231196 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 618468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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: rs35508970; hg19: chr2-46583281;