rs2839576

Positions:

• chr21-42719847-A-G
• chr21-42719847-A-T
• chr21-42719847-A-C

Variant summary

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

The ENST00000291539.11(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 ENST00000291539.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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 = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.263-11923A>G		intron_variant		ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.263-11923A>G		intron_variant		1	NM_002606.3	ENSP00000291539

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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.717

Alfa AF: 0.630 Hom.: 28745

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

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: rs2839576; hg19: chr21-44139957;