2-46356139-C-CG

Position:

• chr2-46356139-C-CG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001430.5(EPAS1):​c.218-12_218-11insG variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (12732 hom., cov: 26)
  • Exomes 𝑓: 0.43 (106152 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPAS1 NM_001430.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 2-46356139-C-CG is Benign according to our data. Variant chr2-46356139-C-CG is described in ClinVar as [Benign]. Clinvar id is 1262112.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.218-12_218-11insG		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-12_257-11insG		splice_polypyrimidine_tract_variant, intron_variant			XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.218-12_218-11insG		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001430.5	ENSP00000263734	P1
EPAS1	ENST00000449347.5	c.218-12_218-11insG		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000406137
EPAS1	ENST00000463191.1	n.25_26insG		non_coding_transcript_exon_variant	1/4	2
EPAS1	ENST00000475822.1	n.409-12_409-11insG		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 59915 AN: 135956 Hom.: 12709 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.476

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.465

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.429 AC: 522506 AN: 1218102 Hom.: 106152 Cov.: 31 AF XY: 0.422 AC XY: 258259 AN XY: 612522

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.441 AC: 59966 AN: 136056 Hom.: 12732 Cov.: 26 AF XY: 0.450 AC XY: 29554 AN XY: 65720

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.471

Alfa AF: 0.156 Hom.: 810

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61586942; hg19: chr2-46583278;