NM_024411.5:c.-20+770A>G

Variant names:

• chr20-1991814-T-C
• rs2281285
• NM_024411.5:c.-20+770A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024411.5(PDYN):​c.-20+770A>G 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 152,030 control chromosomes in the GnomAD database, including 2,867 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 0.17 (2867 hom., cov: 32)
• Consequence: PDYN NM_024411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN	NM_024411.5	c.-20+770A>G		intron_variant	Intron 2 of 3	ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.-20+770A>G		intron_variant	Intron 2 of 3	1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25168 AN: 151912 Hom.: 2876 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.166 AC: 25165 AN: 152030 Hom.: 2867 Cov.: 32 AF XY: 0.173 AC XY: 12851 AN XY: 74326

African (AFR) AF: 0.112 AC: 4653 AN: 41462

American (AMR) AF: 0.206 AC: 3142 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3462

East Asian (EAS) AF: 0.644 AC: 3327 AN: 5166

South Asian (SAS) AF: 0.349 AC: 1676 AN: 4796

European-Finnish (FIN) AF: 0.140 AC: 1475 AN: 10570

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9854 AN: 67970

Other (OTH) AF: 0.168 AC: 355 AN: 2112

Alfa AF: 0.160 Hom.: 9789

Bravo AF: 0.168

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.28
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281285; hg19: chr20-1972460;