20-1994212-T-C

Variant names:

• chr20-1994212-T-C
• rs1997794
• NM_001190899.2:c.-321A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001190899.2(PDYN):​c.-321A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 153,520 control chromosomes in the GnomAD database, including 21,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (21323 hom., cov: 31)
  • Exomes 𝑓: 0.40 (153 hom.)
• Consequence: PDYN NM_001190899.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 20-1994212-T-C is Benign according to our data. Variant chr20-1994212-T-C is described in ClinVar as Benign. ClinVar VariationId is 337846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	NM_001190899.2		c.-321A>G		5_prime_UTR	Exon 1 of 3	NP_001177828.1
	PDYN-AS1	NR_134520.1		n.1253-12720T>C		intron	N/A
	PDYN	NM_024411.5	MANE Select	c.-381A>G		upstream_gene	N/A	NP_077722.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	ENST00000539905.5	TSL:4	c.-321A>G		5_prime_UTR	Exon 1 of 3	ENSP00000440185.1
	PDYN	ENST00000651882.1		c.-378A>G		5_prime_UTR	Exon 1 of 4	ENSP00000498752.1
	PDYN-AS1	ENST00000446562.1	TSL:2	n.1217-12720T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75751 AN: 151842 Hom.: 21280 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.402 AC: 627 AN: 1560 Hom.: 153 Cov.: 0 AF XY: 0.396 AC XY: 343 AN XY: 866

African (AFR) AF: 0.722 AC: 26 AN: 36

American (AMR) AF: 0.450 AC: 9 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 13 AN: 46

East Asian (EAS) AF: 0.803 AC: 143 AN: 178

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 70 AN: 210

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.338 AC: 338 AN: 1000

Other (OTH) AF: 0.409 AC: 27 AN: 66

GnomAD4 genome AF: 0.499 AC: 75857 AN: 151960 Hom.: 21323 Cov.: 31 AF XY: 0.502 AC XY: 37275 AN XY: 74234

African (AFR) AF: 0.750 AC: 31093 AN: 41438

American (AMR) AF: 0.418 AC: 6389 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4388 AN: 5152

South Asian (SAS) AF: 0.576 AC: 2768 AN: 4808

European-Finnish (FIN) AF: 0.384 AC: 4058 AN: 10556

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24528 AN: 67948

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.414 Hom.: 21329

Bravo AF: 0.512

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant cerebellar ataxia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		-0.080
PromoterAI		-0.080	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1997794; hg19: chr20-1974858;