2-182201650-CAAAAA-CAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAA
• rs56413404
• NM_001363871.4:c.1004+33_1004+37dupTTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001363871.4(PDE1A):​c.1004+33_1004+37dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,238,184 control chromosomes in the GnomAD database, including 4,135 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1790 hom., cov: 0)
  • Exomes 𝑓: 0.11 (2345 hom.)
• Consequence: PDE1A NM_001363871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-182201650-C-CAAAAA is Benign according to our data. Variant chr2-182201650-C-CAAAAA is described in ClinVar as Benign. ClinVar VariationId is 1284004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

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+33_1004+37dupTTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+33_1064+37dupTTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+33_1052+37dupTTTTT		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+38insTTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 21023 AN: 136256 Hom.: 1789 Cov.: 0

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0772

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.112 AC: 123395 AN: 1101926 Hom.: 2345 Cov.: 25 AF XY: 0.110 AC XY: 60537 AN XY: 549286

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

African (AFR) AF: 0.106 AC: 2564 AN: 24110

American (AMR) AF: 0.0614 AC: 1250 AN: 20362

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 1133 AN: 18598

East Asian (EAS) AF: 0.0635 AC: 2084 AN: 32842

South Asian (SAS) AF: 0.0610 AC: 3676 AN: 60254

European-Finnish (FIN) AF: 0.126 AC: 4383 AN: 34684

Middle Eastern (MID) AF: 0.0531 AC: 242 AN: 4558

European-Non Finnish (NFE) AF: 0.120 AC: 103244 AN: 859614

Other (OTH) AF: 0.103 AC: 4819 AN: 46904

⚠️ 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: 0.154 AC: 21025 AN: 136258 Hom.: 1790 Cov.: 0 AF XY: 0.151 AC XY: 9776 AN XY: 64864

African (AFR) AF: 0.161 AC: 6036 AN: 37592

American (AMR) AF: 0.106 AC: 1427 AN: 13444

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 282 AN: 3370

East Asian (EAS) AF: 0.0853 AC: 399 AN: 4680

South Asian (SAS) AF: 0.0867 AC: 367 AN: 4232

European-Finnish (FIN) AF: 0.189 AC: 1047 AN: 5552

Middle Eastern (MID) AF: 0.0766 AC: 21 AN: 274

European-Non Finnish (NFE) AF: 0.169 AC: 10901 AN: 64352

Other (OTH) AF: 0.131 AC: 247 AN: 1880

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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;