20-1979552-A-G

Position:

• chr20-1979552-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024411.5(PDYN):​c.*771T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,130 control chromosomes in the GnomAD database, including 11,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11844 hom., cov: 32)
  • Exomes 𝑓: 0.27 (3 hom.)
• Consequence: PDYN NM_024411.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-1979552-A-G is Benign according to our data. Variant chr20-1979552-A-G is described in ClinVar as [Benign]. Clinvar id is 337819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDYN	NM_024411.5	c.*771T>C		3_prime_UTR_variant	4/4	ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305	c.*771T>C		3_prime_UTR_variant	4/4	1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56272 AN: 151922 Hom.: 11809 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.267 AC: 24 AN: 90 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 10 AN XY: 40

Gnomad4 AMR exome AF: 0.375

Gnomad4 NFE exome AF: 0.256

GnomAD4 genome AF: 0.371 AC: 56373 AN: 152040 Hom.: 11844 Cov.: 32 AF XY: 0.377 AC XY: 28038 AN XY: 74322

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.360

Alfa AF: 0.277 Hom.: 3626

Bravo AF: 0.380

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spinocerebellar ataxia type 23 Benign:1

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.56

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: rs910079; hg19: chr20-1960198;