20-1994212-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001190899.2(PDYN):​c.-321A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDYN NM_001190899.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	NM_001190899.2		c.-321A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001177828.1	P01213
	PDYN	NM_001190899.2		c.-321A>T		5_prime_UTR	Exon 1 of 3	NP_001177828.1	P01213
	PDYN-AS1	NR_134520.1		n.1253-12720T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	ENST00000539905.5	TSL:4	c.-321A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000651882.1		c.-378A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000498752.1	A0A494C0X3
	PDYN	ENST00000539905.5	TSL:4	c.-321A>T		5_prime_UTR	Exon 1 of 3	ENSP00000440185.1	P01213

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1566 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 870

African (AFR) AF: 0.00 AC: 0 AN: 36

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 46

East Asian (EAS) AF: 0.00 AC: 0 AN: 178

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002

Other (OTH) AF: 0.00 AC: 0 AN: 68

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		-0.080
PromoterAI		-0.085	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;