chr20-1994400-AAGAGAGAGAG-A

Variant names:

• chr20-1994400-AAGAGAGAGAG-A
• rs34535593
• ENST00000446562.1:n.1217-12531_1217-12522delAGAGAGAGAG

Variant summary

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

The ENST00000446562.1(PDYN-AS1):​n.1217-12531_1217-12522delAGAGAGAGAG variant causes a 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: 30)
• Consequence: PDYN-AS1 ENST00000446562.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 2 publications found

Genes affected

PDYN-AS1 (HGNC:53462): (PDYN antisense RNA 1)

PDYN (HGNC:8820): (prodynorphin) The protein encoded by this gene is a preproprotein that is proteolytically processed to form the secreted opioid peptides beta-neoendorphin, dynorphin, leu-enkephalin, rimorphin, and leumorphin. These peptides are ligands for the kappa-type of opioid receptor. Dynorphin is involved in modulating responses to several psychoactive substances, including cocaine. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

PDYN Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 23

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446562.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN-AS1	NR_134520.1		n.1253-12522_1253-12513delGAGAGAGAGA		intron	N/A
	PDYN	NM_001190899.2		c.-519_-510delCTCTCTCTCT		upstream_gene	N/A	NP_001177828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN-AS1	ENST00000446562.1	TSL:2	n.1217-12531_1217-12522delAGAGAGAGAG		intron	N/A
	PDYN-AS1	ENST00000651021.1		n.475+28058_475+28067delAGAGAGAGAG		intron	N/A
	PDYN	ENST00000539905.5	TSL:4	c.-519_-510delCTCTCTCTCT		upstream_gene	N/A	ENSP00000440185.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 6

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs34535593; hg19: chr20-1975046;