2-182201650-CAAAAA-CAAAAAAAAAAA

Variant names:

• chr2-182201650-C-CAAAAAA
• rs56413404
• NM_001363871.4:c.1004+32_1004+37dupTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001363871.4(PDE1A):​c.1004+32_1004+37dupTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0769 in 1,104,006 control chromosomes in the GnomAD database, including 1,107 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (613 hom., cov: 0)
  • Exomes 𝑓: 0.077 (1107 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 2-182201650-C-CAAAAAA is Benign according to our data. Variant chr2-182201650-C-CAAAAAA is described in ClinVar as Benign. ClinVar VariationId is 1265372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 1107 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+32_1004+37dupTTTTTT		intron	N/A	NP_001350800.1	P54750-6
	PDE1A	NM_001258312.3		c.1064+32_1064+37dupTTTTTT		intron	N/A	NP_001245241.1
	PDE1A	NM_001395258.2		c.1052+32_1052+37dupTTTTTT		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+38insTTTTTT		intron	N/A	ENSP00000386767.1	P54750-6
	PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTTT		intron	N/A	ENSP00000410309.1	P54750-4
	PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTTT		intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 11098 AN: 136364 Hom.: 613 Cov.: 0

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.0921

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0816

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0855

GnomAD4 exome AF: 0.0769 AC: 84878 AN: 1104006 Hom.: 1107 Cov.: 25 AF XY: 0.0770 AC XY: 42366 AN XY: 550066

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

African (AFR) AF: 0.0247 AC: 606 AN: 24562

American (AMR) AF: 0.0631 AC: 1273 AN: 20188

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 1099 AN: 18408

East Asian (EAS) AF: 0.0601 AC: 1954 AN: 32496

South Asian (SAS) AF: 0.0657 AC: 3929 AN: 59782

European-Finnish (FIN) AF: 0.0738 AC: 2576 AN: 34916

Middle Eastern (MID) AF: 0.0541 AC: 244 AN: 4512

European-Non Finnish (NFE) AF: 0.0809 AC: 69752 AN: 862162

Other (OTH) AF: 0.0733 AC: 3445 AN: 46980

⚠️ 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: 0.0814 AC: 11097 AN: 136364 Hom.: 613 Cov.: 0 AF XY: 0.0799 AC XY: 5188 AN XY: 64894

African (AFR) AF: 0.0235 AC: 888 AN: 37728

American (AMR) AF: 0.0841 AC: 1129 AN: 13428

Ashkenazi Jewish (ASJ) AF: 0.0921 AC: 310 AN: 3366

East Asian (EAS) AF: 0.0906 AC: 423 AN: 4670

South Asian (SAS) AF: 0.103 AC: 434 AN: 4228

European-Finnish (FIN) AF: 0.0718 AC: 399 AN: 5560

Middle Eastern (MID) AF: 0.0852 AC: 23 AN: 270

European-Non Finnish (NFE) AF: 0.112 AC: 7234 AN: 64350

Other (OTH) AF: 0.0850 AC: 160 AN: 1882

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;