rs2304418

Positions:

• chr15-85097752-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002605.3(PDE8A):​c.853-196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 551,636 control chromosomes in the GnomAD database, including 18,614 homozygotes. 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: 𝑓 0.21 (4301 hom., cov: 32)
  • Exomes 𝑓: 0.25 (14313 hom.)
• Consequence: PDE8A NM_002605.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

Genes affected

PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE8A	NM_002605.3	c.853-196T>C		intron_variant		ENST00000394553.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE8A	ENST00000394553.6	c.853-196T>C		intron_variant		1	NM_002605.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31551 AN: 152088 Hom.: 4309 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.252 AC: 100714 AN: 399428 Hom.: 14313 AF XY: 0.249 AC XY: 52826 AN XY: 211818

Gnomad4 AFR exome AF: 0.0494

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.0379

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.207 AC: 31524 AN: 152208 Hom.: 4301 Cov.: 32 AF XY: 0.206 AC XY: 15324 AN XY: 74414

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.241

Alfa AF: 0.265 Hom.: 2704

Bravo AF: 0.194

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.81

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: rs2304418; hg19: chr15-85640983;