rs267606940

Variant names:

• chr20-1980456-A-C
• NM_024411.5:c.632T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-1980456-A-C
• chr20-1980456-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_024411.5(PDYN):​c.632T>G​(p.Leu211Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PDYN NM_024411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.66

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 Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a peptide Big dynorphin (size 31) in uniprot entity PDYN_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_024411.5
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-1980456-A-C is Pathogenic according to our data. Variant chr20-1980456-A-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN	NM_024411.5	c.632T>G	p.Leu211Trp	missense_variant	Exon 4 of 4	ENST00000217305.3	NP_077722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3	c.632T>G	p.Leu211Trp	missense_variant	Exon 4 of 4	1	NM_024411.5	ENSP00000217305.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Benign	0.96
DEOGEN2	Uncertain	0.72	D;D;D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	.;D;.
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.56
MutPred		0.61		Gain of MoRF binding (P = 0.0676);Gain of MoRF binding (P = 0.0676);Gain of MoRF binding (P = 0.0676);
MVP		0.93
MPC		0.26
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.49
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1961102;