Genetic Variant PDE1A:c.1004+37_1004+38insTTTTTTTTTTTTTTT (chr2-182201650-C-CAAAAAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001363871.4(PDE1A):c.1004+37_1004+38insTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDE1A
NM_001363871.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.543

Publications

1 publications found

Variant links:

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]

PDE1A links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE1A	NM_001363871.4	MANE Select	c.1004+37_1004+38insTTTTTTTTTTTTTTT	intron	N/A	NP_001350800.1	P54750-6
PDE1A	NM_001258312.3		c.1064+37_1064+38insTTTTTTTTTTTTTTT	intron	N/A	NP_001245241.1
PDE1A	NM_001395258.2		c.1052+37_1052+38insTTTTTTTTTTTTTTT	intron	N/A	NP_001382187.1	P54750-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE1A	ENST00000409365.6	TSL:5 MANE Select	c.1004+37_1004+38insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000386767.1	P54750-6
PDE1A	ENST00000435564.6	TSL:1	c.1052+37_1052+38insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000410309.1	P54750-4
PDE1A	ENST00000410103.2	TSL:1	c.1052+37_1052+38insTTTTTTTTTTTTTTT	intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes

AF:

0.00000731

AC:

AN:

136746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000345

AC:

AN:

1131398

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

564274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24914

American (AMR)

AF:

0.0000962

AC:

AN:

20788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19088

East Asian (EAS)

AF:

0.00

AC:

AN:

33676

South Asian (SAS)

AF:

0.0000655

AC:

AN:

61046

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

35992

Middle Eastern (MID)

AF:

0.000433

AC:

AN:

4618

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

882902

Other (OTH)

AF:

0.0000413

AC:

AN:

48374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000731

AC:

AN:

136744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65102

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

37774

American (AMR)

AF:

0.00

AC:

AN:

13492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3372

East Asian (EAS)

AF:

0.00

AC:

AN:

4684

South Asian (SAS)

AF:

0.00

AC:

AN:

4252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64534

Other (OTH)

AF:

0.00

AC:

AN:

1886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.54

Splicing

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

Publications

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2-182201650-CAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over