chr21-42756452-A-G

Position:

• chr21-42756452-A-G

Variant summary

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

The NM_002606.3(PDE9A):​c.810+2388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,054 control chromosomes in the GnomAD database, including 17,430 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 0.47 (17430 hom., cov: 33)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.810+2388A>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.810+2388A>G		intron_variant		1	NM_002606.3	ENSP00000291539

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72001 AN: 151936 Hom.: 17425 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.474 AC: 72023 AN: 152054 Hom.: 17430 Cov.: 33 AF XY: 0.468 AC XY: 34794 AN XY: 74318

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.442

Alfa AF: 0.508 Hom.: 4047

Bravo AF: 0.468

Asia WGS AF: 0.303 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.34
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs729861; hg19: chr21-44176562;