chr2-46356142-C-CGCTCT

Position:

• chr2-46356142-C-CGCTCT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000263734.5(EPAS1):​c.218-9_218-8insGCTCT 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: EPAS1 ENST00000263734.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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]

EPAS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-46356142-C-CGCTCT is Benign according to our data. Variant chr2-46356142-C-CGCTCT is described in ClinVar as [Likely_benign]. Clinvar id is 2776123.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.218-9_218-8insGCTCT		splice_region_variant, intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-9_257-8insGCTCT		splice_region_variant, intron_variant			XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.218-9_218-8insGCTCT		splice_region_variant, intron_variant		1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.218-9_218-8insGCTCT		splice_region_variant, intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000463191.1	n.28_29insGCTCT		non_coding_transcript_exon_variant	1/4	2
EPAS1	ENST00000475822.1	n.409-9_409-8insGCTCT		splice_region_variant, intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

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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;