2-182201650-CAAAAA-CAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001363871.4(PDE1A):​c.1004+34_1004+37dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,252,410 control chromosomes in the GnomAD database, including 404 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (9 hom., cov: 0)
  • Exomes 𝑓: 0.039 (395 hom.)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 9 gene

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+37dupTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+34_1064+37dupTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+34_1052+37dupTTTT		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+38insTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 434 AN: 136732 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.0272

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.00281

Gnomad FIN AF: 0.00590

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00373

GnomAD4 exome AF: 0.0390 AC: 43553 AN: 1115680 Hom.: 395 Cov.: 25 AF XY: 0.0388 AC XY: 21607 AN XY: 556248

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

African (AFR) AF: 0.0219 AC: 539 AN: 24624

American (AMR) AF: 0.0256 AC: 525 AN: 20520

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 358 AN: 18872

East Asian (EAS) AF: 0.0526 AC: 1732 AN: 32920

South Asian (SAS) AF: 0.0392 AC: 2355 AN: 60126

European-Finnish (FIN) AF: 0.0500 AC: 1764 AN: 35270

Middle Eastern (MID) AF: 0.0250 AC: 114 AN: 4564

European-Non Finnish (NFE) AF: 0.0395 AC: 34433 AN: 871186

Other (OTH) AF: 0.0364 AC: 1733 AN: 47598

⚠️ 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 AF: 0.00318 AC: 435 AN: 136730 Hom.: 9 Cov.: 0 AF XY: 0.00340 AC XY: 221 AN XY: 65094

African (AFR) AF: 0.00164 AC: 62 AN: 37774

American (AMR) AF: 0.00141 AC: 19 AN: 13494

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3372

East Asian (EAS) AF: 0.0177 AC: 83 AN: 4682

South Asian (SAS) AF: 0.00282 AC: 12 AN: 4252

European-Finnish (FIN) AF: 0.00590 AC: 33 AN: 5590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00301 AC: 194 AN: 64524

Other (OTH) AF: 0.00371 AC: 7 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;