2-182201650-CAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAAAAA
• rs56413404
• NM_001363871.4:c.1004+30_1004+37dupTTTTTTTT

Variant summary

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

The NM_001363871.4(PDE1A):​c.1004+30_1004+37dupTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0054 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 1 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 0 ACMG points.

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+30_1004+37dupTTTTTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+30_1064+37dupTTTTTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+30_1052+37dupTTTTTTTT		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+37_1004+38insTTTTTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 217 AN: 136732 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000716

Gnomad AMI AF: 0.00113

Gnomad AMR AF: 0.00326

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000639

Gnomad SAS AF: 0.000702

Gnomad FIN AF: 0.00107

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.00160

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00541 AC: 6094 AN: 1125974 Hom.: 23 Cov.: 25 AF XY: 0.00543 AC XY: 3047 AN XY: 561588

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000844 AC: 21 AN: 24878

American (AMR) AF: 0.0114 AC: 236 AN: 20624

Ashkenazi Jewish (ASJ) AF: 0.00597 AC: 113 AN: 18940

East Asian (EAS) AF: 0.00994 AC: 331 AN: 33286

South Asian (SAS) AF: 0.00405 AC: 246 AN: 60810

European-Finnish (FIN) AF: 0.00979 AC: 348 AN: 35552

Middle Eastern (MID) AF: 0.00240 AC: 11 AN: 4588

European-Non Finnish (NFE) AF: 0.00514 AC: 4517 AN: 879202

Other (OTH) AF: 0.00563 AC: 271 AN: 48094

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00159 AC: 217 AN: 136730 Hom.: 1 Cov.: 0 AF XY: 0.00129 AC XY: 84 AN XY: 65098

African (AFR) AF: 0.000715 AC: 27 AN: 37770

American (AMR) AF: 0.00326 AC: 44 AN: 13492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.000640 AC: 3 AN: 4684

South Asian (SAS) AF: 0.000706 AC: 3 AN: 4252

European-Finnish (FIN) AF: 0.00107 AC: 6 AN: 5592

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.00200 AC: 129 AN: 64524

Other (OTH) AF: 0.00159 AC: 3 AN: 1886

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs56413404; hg19: chr2-183066377;