rs6045819

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024411.5(PDYN):c.600T>C(p.His200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,502 control chromosomes in the GnomAD database, including 13,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2318 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11033 hom. )

Consequence

PDYN
NM_024411.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.93

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 20-1980488-A-G is Benign according to our data. Variant chr20-1980488-A-G is described in ClinVar as [Benign]. Clinvar id is 337834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-1980488-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5 linkuse as main transcript	c.600T>C	p.His200=	synonymous_variant	4/4	ENST00000217305.3	NP_077722.1
PDYN-AS1	NR_134520.1 linkuse as main transcript	n.1252+14145A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3 linkuse as main transcript	c.600T>C	p.His200=	synonymous_variant	4/4	1	NM_024411.5	ENSP00000217305	P1
PDYN-AS1	ENST00000651021.1 linkuse as main transcript	n.475+14145A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23448

AN:

151562

Hom.:

2312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.0799

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.106

AC:

26563

AN:

251350

Hom.:

1894

AF XY:

0.103

AC XY:

13935

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0661

Gnomad FIN exome

AF:

0.0795

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.115

AC:

168373

AN:

1461820

Hom.:

11033

Cov.:

AF XY:

0.114

AC XY:

82707

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.0832

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0693

Gnomad4 FIN exome

AF:

0.0814

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.155

AC:

23480

AN:

151682

Hom.:

2318

Cov.:

AF XY:

0.151

AC XY:

11159

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.00156

Gnomad4 SAS

AF:

0.0638

Gnomad4 FIN

AF:

0.0799

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.127

Hom.:

1915

Bravo

AF:

0.165

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 23

Benign:4

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.012

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over