chr2-46356142-C-CGCTCT

Variant names:

• chr2-46356142-C-CGCTCT
• rs35508970
• NM_001430.5:c.218-9_218-8insGCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001430.5(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 NM_001430.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628
• Publications: 5 publications found

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]

LINC01820 (HGNC:52625): (long intergenic non-protein coding RNA 1820)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 2776123.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001430.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	NM_001430.5	MANE Select	c.218-9_218-8insGCTCT		splice_region intron	N/A	NP_001421.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	ENST00000263734.5	TSL:1 MANE Select	c.218-9_218-8insGCTCT		splice_region intron	N/A	ENSP00000263734.3	Q99814
	EPAS1	ENST00000861819.1		c.218-9_218-8insGCTCT		splice_region intron	N/A	ENSP00000531878.1
	EPAS1	ENST00000861817.1		c.212-9_212-8insGCTCT		splice_region intron	N/A	ENSP00000531876.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35508970; hg19: chr2-46583281;