2-182201650-CAAAAA-CA

Variant names:

• chr2-182201650-CAAAA-C
• rs56413404
• NM_001363871.4:c.1004+34_1004+37delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001363871.4(PDE1A):​c.1004+34_1004+37delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 1,131,588 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363871.4. 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.1004+34_1004+37delTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+34_1064+37delTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+34_1052+37delTTTT		intron	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1004+34_1004+37delTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+34_1052+37delTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+34_1052+37delTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000265 AC: 3 AN: 1131588 Hom.: 0 AF XY: 0.00000354 AC XY: 2 AN XY: 564374

African (AFR) AF: 0.00 AC: 0 AN: 24916

American (AMR) AF: 0.00 AC: 0 AN: 20796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19088

East Asian (EAS) AF: 0.00 AC: 0 AN: 33686

South Asian (SAS) AF: 0.00 AC: 0 AN: 61072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00000340 AC: 3 AN: 883026

Other (OTH) AF: 0.00 AC: 0 AN: 48384

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

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

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;