rs2235749

chr20-1979293-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.58

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)

ACMG classification

Verdict is Benign. Variant got -12 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 id is 337814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDYN	NM_024411.5	c.*1030C>T		3_prime_UTR_variant	4/4	ENST00000217305.3
PDYN-AS1	NR_134520.1	n.1252+12950G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDYN	ENST00000217305.3	c.*1030C>T		3_prime_UTR_variant	4/4	1	NM_024411.5	P1
PDYN-AS1	ENST00000651021.1	n.475+12950G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56197 AN: 151886 Hom.: 11774 Cov.: 32

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.: 52 Cov.: 0 AF XY: 0.372 AC XY: 111 AN XY: 298

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.807

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.370 AC: 56297 AN: 152004 Hom.: 11808 Cov.: 32 AF XY: 0.377 AC XY: 28022 AN XY: 74302

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.359

Alfa AF: 0.297 Hom.: 7063

Bravo AF: 0.379

Asia WGS AF: 0.685 AC: 2381 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	14
Dann	Benign	0.83

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: rs2235749; hg19: chr20-1959939;