21-42719847-A-G

Variant names:

• chr21-42719847-A-G
• rs2839576
• NM_002606.3:c.263-11923A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002606.3(PDE9A):​c.263-11923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,902 control chromosomes in the GnomAD database, including 40,137 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 0.71 (40137 hom., cov: 30)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.263-11923A>G		intron_variant	Intron 4 of 19	ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.263-11923A>G		intron_variant	Intron 4 of 19	1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107724 AN: 151784 Hom.: 40077 Cov.: 30

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.710 AC: 107835 AN: 151902 Hom.: 40137 Cov.: 30 AF XY: 0.705 AC XY: 52357 AN XY: 74228

African (AFR) AF: 0.928 AC: 38461 AN: 41448

American (AMR) AF: 0.576 AC: 8776 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2433 AN: 3468

East Asian (EAS) AF: 0.942 AC: 4868 AN: 5168

South Asian (SAS) AF: 0.749 AC: 3600 AN: 4808

European-Finnish (FIN) AF: 0.578 AC: 6082 AN: 10516

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41285 AN: 67940

Other (OTH) AF: 0.717 AC: 1511 AN: 2106

Alfa AF: 0.643 Hom.: 39944

Bravo AF: 0.722

Asia WGS AF: 0.863 AC: 3001 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	5.1
DANN	Benign	0.79
PhyloP100		-0.43
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2839576; hg19: chr21-44139957;