rs2281285

Positions:

• chr20-1991814-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
PDYN	NM_024411.5	c.-20+770A>G		intron_variant		ENST00000217305.3
PDYN-AS1	NR_134520.1	n.1253-15118T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDYN	ENST00000217305.3	c.-20+770A>G		intron_variant		1	NM_024411.5	P1
PDYN-AS1	ENST00000651021.1	n.475+25471T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.168

Alfa AF: 0.158 Hom.: 4131

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

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: rs2281285; hg19: chr20-1972460;