20-1983050-AG-AGGG

Variant names:

• chr20-1983050-A-AGG
• rs761385412
• NM_024411.5:c.33_34dupCC

Variant summary

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

The NM_024411.5(PDYN):​c.33_34dupCC​(p.Leu12ProfsTer21) variant causes a frameshift 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: 32)
• Consequence: PDYN NM_024411.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

Genes affected

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

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: NM_024411.5. 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	NM_024411.5	MANE Select	c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 3 of 4	NP_077722.1
	PDYN	NM_001190892.1		c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 2 of 3	NP_001177821.1
	PDYN	NM_001190898.3		c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 3 of 4	NP_001177827.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	ENST00000217305.3	TSL:1 MANE Select	c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 3 of 4	ENSP00000217305.2
	PDYN	ENST00000539905.5	TSL:4	c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 2 of 3	ENSP00000440185.1
	PDYN	ENST00000540134.5	TSL:4	c.33_34dupCC	p.Leu12ProfsTer21	frameshift	Exon 3 of 4	ENSP00000442259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs761385412; hg19: chr20-1963696;