2-182201650-CAAAAA-CAAAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAAAA
• rs56413404
• NM_001363871.4:c.1004+31_1004+37dupTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001363871.4(PDE1A):​c.1004+31_1004+37dupTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,113,626 control chromosomes in the GnomAD database, including 294 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (150 hom., cov: 0)
  • Exomes 𝑓: 0.031 (294 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1A	NM_001363871.4	c.1004+31_1004+37dupTTTTTTT		intron_variant	Intron 9 of 14	ENST00000409365.6	NP_001350800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1A	ENST00000409365.6	c.1004+37_1004+38insTTTTTTT		intron_variant	Intron 9 of 14	5	NM_001363871.4	ENSP00000386767.1

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 4823 AN: 136484 Hom.: 148 Cov.: 0

Gnomad AFR AF: 0.00838

Gnomad AMI AF: 0.00113

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0702

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.0503

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0433

GnomAD4 exome AF: 0.0305 AC: 33997 AN: 1113626 Hom.: 294 Cov.: 25 AF XY: 0.0306 AC XY: 16972 AN XY: 555216

Gnomad4 AFR exome AF: 0.00597

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.0624

Gnomad4 SAS exome AF: 0.0211

Gnomad4 FIN exome AF: 0.0588

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0323

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0353 AC: 4823 AN: 136482 Hom.: 150 Cov.: 0 AF XY: 0.0370 AC XY: 2401 AN XY: 64954

Gnomad4 AFR AF: 0.00837

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.0702

Gnomad4 EAS AF: 0.0695

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;