21-42688133-C-G

Variant names:

• chr21-42688133-C-G
• rs13047947
• NM_002606.3:c.218+139C>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.218+139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 730,018 control chromosomes in the GnomAD database, including 10,552 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 0.15 (1948 hom., cov: 32)
  • Exomes 𝑓: 0.16 (8604 hom.)
• Consequence: PDE9A NM_002606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE9A	NM_002606.3	c.218+139C>G		intron_variant	Intron 3 of 19	ENST00000291539.11	NP_002597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE9A	ENST00000291539.11	c.218+139C>G		intron_variant	Intron 3 of 19	1	NM_002606.3	ENSP00000291539.6

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23505 AN: 152064 Hom.: 1950 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.164 AC: 94642 AN: 577836 Hom.: 8604 AF XY: 0.164 AC XY: 50121 AN XY: 306306

African (AFR) AF: 0.133 AC: 2160 AN: 16274

American (AMR) AF: 0.0840 AC: 2770 AN: 32976

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 4218 AN: 18220

East Asian (EAS) AF: 0.333 AC: 10667 AN: 31990

South Asian (SAS) AF: 0.135 AC: 8082 AN: 59934

European-Finnish (FIN) AF: 0.147 AC: 4865 AN: 33010

Middle Eastern (MID) AF: 0.181 AC: 722 AN: 3986

European-Non Finnish (NFE) AF: 0.160 AC: 55986 AN: 350344

Other (OTH) AF: 0.166 AC: 5172 AN: 31102

GnomAD4 genome AF: 0.155 AC: 23524 AN: 152182 Hom.: 1948 Cov.: 32 AF XY: 0.154 AC XY: 11471 AN XY: 74406

African (AFR) AF: 0.132 AC: 5482 AN: 41526

American (AMR) AF: 0.116 AC: 1776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 796 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1755 AN: 5166

South Asian (SAS) AF: 0.144 AC: 694 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10596

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10937 AN: 68002

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.0661 Hom.: 75

Bravo AF: 0.155

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13047947; hg19: chr21-44108243; COSMIC: COSV107329518;