21-42752803-T-C

Position:

• chr21-42752803-T-C

Variant summary

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

The NM_002606.3(PDE9A):​c.736-1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,190 control chromosomes in the GnomAD database, including 4,651 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 0.22 (4651 hom., cov: 33)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

PDE9A (HGNC:8795): (phosphodiesterase 9A) The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE9A	NM_002606.3	c.736-1187T>C		intron_variant		ENST00000291539.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE9A	ENST00000291539.11	c.736-1187T>C		intron_variant		1	NM_002606.3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34238 AN: 152072 Hom.: 4655 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34235 AN: 152190 Hom.: 4651 Cov.: 33 AF XY: 0.222 AC XY: 16551 AN XY: 74418

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.252

Alfa AF: 0.280 Hom.: 8026

Bravo AF: 0.227

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.56

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: rs2284967; hg19: chr21-44172913;