rs6045819

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.His200His) 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

2

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

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 rank MANE Protein UniProt
PDYNNM_024411.5 linkc.600T>C p.His200His synonymous_variant Exon 4 of 4 ENST00000217305.3 NP_077722.1 P01213

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDYNENST00000217305.3 linkc.600T>C p.His200His synonymous_variant Exon 4 of 4 1 NM_024411.5 ENSP00000217305.2 P01213

Frequencies

GnomAD3 genomes
AF:
0.155
AC:
23448
AN:
151562
Hom.:
2312
Cov.:
31
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.:
33
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.:
31
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
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Sep 21, 2015
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 10, 2014
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 04, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Sep 20, 2019
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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.

Other links and lift over

dbSNP: rs6045819; hg19: chr20-1961134; COSMIC: COSV54103447; API