rs2235751

Positions:

• chr20-1989288-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024411.5(PDYN):​c.-20+3296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,976 control chromosomes in the GnomAD database, including 14,937 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (14937 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5	c.-20+3296T>C		intron_variant		ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.-20+3296T>C		intron_variant		1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60692 AN: 151858 Hom.: 14918 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.400 AC: 60773 AN: 151976 Hom.: 14937 Cov.: 32 AF XY: 0.404 AC XY: 29990 AN XY: 74286

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.357

Alfa AF: 0.278 Hom.: 13406

Bravo AF: 0.412

Asia WGS AF: 0.691 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2235751; hg19: chr20-1969934; COSMIC: COSV99452838;