rs6035222

Positions:

• chr20-1982767-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024411.5(PDYN):​c.129+189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,118 control chromosomes in the GnomAD database, including 2,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2656 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-1982767-G-A is Benign according to our data. Variant chr20-1982767-G-A is described in ClinVar as [Benign]. Clinvar id is 1260880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5	c.129+189C>T		intron_variant		ENST00000217305.3	NP_077722.1
PDYN-AS1	NR_134520.1	n.1252+16424G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.129+189C>T		intron_variant		1	NM_024411.5	ENSP00000217305	P1
PDYN-AS1	ENST00000651021.1	n.475+16424G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25259 AN: 152000 Hom.: 2645 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.166 AC: 25314 AN: 152118 Hom.: 2656 Cov.: 32 AF XY: 0.161 AC XY: 11968 AN XY: 74392

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.181

Alfa AF: 0.146 Hom.: 272

Bravo AF: 0.176

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.51

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: rs6035222; hg19: chr20-1963413;