Genetic Variant PDYN:c.*1030C>T (chr20-1979293-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_024411.5(PDYN):c.*1030C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,584 control chromosomes in the GnomAD database, including 11,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11808 hom., cov: 32)

Exomes 𝑓: 0.36 ( 52 hom. )

Consequence

PDYN
NM_024411.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.58

Publications

35 publications found

Variant links:

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 links:

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

PDYN-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 20-1979293-G-A is Benign according to our data. Variant chr20-1979293-G-A is described in ClinVar as Benign. ClinVar VariationId is 337814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	NM_024411.5	MANE Select	c.*1030C>T	3_prime_UTR	Exon 4 of 4	NP_077722.1	P01213
PDYN	NM_001190892.1		c.*1030C>T	3_prime_UTR	Exon 3 of 3	NP_001177821.1	P01213
PDYN	NM_001190898.3		c.*1030C>T	3_prime_UTR	Exon 4 of 4	NP_001177827.1	P01213

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	ENST00000217305.3	TSL:1 MANE Select	c.*1030C>T	3_prime_UTR	Exon 4 of 4	ENSP00000217305.2	P01213
PDYN	ENST00000539905.5	TSL:4	c.*1030C>T	3_prime_UTR	Exon 3 of 3	ENSP00000440185.1	P01213
PDYN	ENST00000540134.5	TSL:4	c.*1030C>T	3_prime_UTR	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56197

AN:

151886

Hom.:

11774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.357

AC:

207

AN:

580

Hom.:

Cov.:

AF XY:

0.372

AC XY:

111

AN XY:

298

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.429

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

AN:

East Asian (EAS)

AF:

0.807

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.348

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.231

AC:

AN:

342

Other (OTH)

AF:

0.385

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.370

AC:

56297

AN:

152004

Hom.:

11808

Cov.:

AF XY:

0.377

AC XY:

28022

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.496

AC:

20570

AN:

41442

American (AMR)

AF:

0.341

AC:

5218

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3470

East Asian (EAS)

AF:

0.843

AC:

4361

AN:

5174

South Asian (SAS)

AF:

0.526

AC:

2528

AN:

4810

European-Finnish (FIN)

AF:

0.303

AC:

3194

AN:

10540

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18324

AN:

67972

Other (OTH)

AF:

0.359

AC:

758

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1710

3420

5130

6840

8550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.304

Hom.:

9716

Bravo

AF:

0.379

Asia WGS

AF:

0.685

AC:

2381

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Spinocerebellar ataxia type 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over