rs17649232

Variant names:

• chr2-182140011-T-C
• rs17649232
• ENST00000462938.6:n.*4603A>G

Variant summary

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

The ENST00000462938.6(PDE1A):​n.*4603A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,320 control chromosomes in the GnomAD database, including 298 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 0.054 (298 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: PDE1A ENST00000462938.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 4 publications found

Genes affected

PDE1A (HGNC:8774): (phosphodiesterase 1A) Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462938.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	NM_001363871.4	MANE Select	c.*3071A>G		downstream_gene	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.*3071A>G		downstream_gene	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.*3071A>G		downstream_gene	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000462938.6	TSL:4	n.*4603A>G		non_coding_transcript_exon	Exon 16 of 16	ENSP00000512256.1	A0A8Q3WKY5
	PDE1A	ENST00000462938.6	TSL:4	n.*4603A>G		3_prime_UTR	Exon 16 of 16	ENSP00000512256.1	A0A8Q3WKY5
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.*3071A>G		downstream_gene	N/A	ENSP00000386767.1	P54750-6

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8175 AN: 152194 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0537 AC: 8173 AN: 152312 Hom.: 298 Cov.: 33 AF XY: 0.0534 AC XY: 3977 AN XY: 74468

African (AFR) AF: 0.0176 AC: 732 AN: 41576

American (AMR) AF: 0.0439 AC: 672 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5192

South Asian (SAS) AF: 0.0557 AC: 269 AN: 4828

European-Finnish (FIN) AF: 0.0699 AC: 742 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5455 AN: 68008

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0728 Hom.: 288

Bravo AF: 0.0491

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17649232; hg19: chr2-183004738;