Genetic Variant PDYN-AS1:n.1217-12531_1217-12528delAGAG (chr20-1994400-AAGAG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000446562.1(PDYN-AS1):n.1217-12531_1217-12528delAGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 150,394 control chromosomes in the GnomAD database, including 1,235 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1235 hom., cov: 30)

Exomes 𝑓: 0.055 ( 0 hom. )

Consequence

PDYN-AS1
ENST00000446562.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.741

Publications

2 publications found

Variant links:

Genes affected

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

PDYN-AS1 links:

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 23
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

PDYN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446562.1. 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-AS1	NR_134520.1		n.1253-12516_1253-12513delGAGA		intron	N/A
	PDYN	NM_001190899.2		c.-513_-510delCTCT		upstream_gene	N/A	NP_001177828.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDYN-AS1	ENST00000446562.1	TSL:2	n.1217-12531_1217-12528delAGAG	intron	N/A
PDYN-AS1	ENST00000651021.1		n.475+28058_475+28061delAGAG	intron	N/A
PDYN	ENST00000539905.5	TSL:4	c.-513_-510delCTCT	upstream_gene	N/A	ENSP00000440185.1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

17962

AN:

150150

Hom.:

1234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.0716

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0829

Gnomad MID

AF:

0.189

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.0548

AC:

AN:

146

Hom.:

AF XY:

0.0686

AC XY:

AN XY:

102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0667

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0556

AC:

AN:

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.120

AC:

17988

AN:

150248

Hom.:

1235

Cov.:

AF XY:

0.123

AC XY:

9003

AN XY:

73338

show subpopulations

African (AFR)

AF:

0.157

AC:

6444

AN:

41112

American (AMR)

AF:

0.193

AC:

2912

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

389

AN:

3436

East Asian (EAS)

AF:

0.145

AC:

745

AN:

5140

South Asian (SAS)

AF:

0.147

AC:

693

AN:

4728

European-Finnish (FIN)

AF:

0.0829

AC:

840

AN:

10128

Middle Eastern (MID)

AF:

0.190

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0828

AC:

5570

AN:

67310

Other (OTH)

AF:

0.132

AC:

275

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

776

1552

2328

3104

3880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.74

Splicing

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

Publications

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20-1994400-AAGAGAGAGAG-AAGAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over