Genetic Variant PDE1A:c.1516+17595_1516+17598dupTTTT (chr2-182168293-G-GAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001003683.3(PDE1A):c.1565-7_1565-4dupTTTT variant causes a splice region, 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 0.0000074 ( 0 hom., cov: 25)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDE1A
NM_001003683.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659

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:

Genome browser will be placed here

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_001003683.3. 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.1516+17595_1516+17598dupTTTT	intron	N/A	NP_001350800.1	P54750-6
PDE1A	NM_001258312.3		c.1576+17595_1576+17598dupTTTT	intron	N/A	NP_001245241.1
PDE1A	NM_001395258.2		c.1564+17595_1564+17598dupTTTT	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.1516+17598_1516+17599insTTTT	intron	N/A	ENSP00000386767.1	P54750-6
PDE1A	ENST00000435564.6	TSL:1	c.1564+17598_1564+17599insTTTT	intron	N/A	ENSP00000410309.1	P54750-4
PDE1A	ENST00000410103.2	TSL:1	c.1565-4_1565-3insTTTT	splice_region intron	N/A	ENSP00000387037.1	P54750-1

Frequencies

GnomAD3 genomes

AF:

0.00000736

AC:

AN:

135894

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:

0.000135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.49e-7

AC:

AN:

1178384

Hom.:

Cov.:

AF XY:

0.00000171

AC XY:

AN XY:

586092

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25850

American (AMR)

AF:

0.00

AC:

AN:

28138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20328

East Asian (EAS)

AF:

0.00

AC:

AN:

32990

South Asian (SAS)

AF:

0.0000155

AC:

AN:

64416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

911504

Other (OTH)

AF:

0.00

AC:

AN:

48412

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000736

AC:

AN:

135894

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65384

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:

37126

American (AMR)

AF:

0.00

AC:

AN:

13826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3210

East Asian (EAS)

AF:

0.00

AC:

AN:

4850

South Asian (SAS)

AF:

0.00

AC:

AN:

4396

European-Finnish (FIN)

AF:

0.000135

AC:

AN:

7382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62146

Other (OTH)

AF:

0.00

AC:

AN:

1832

⚠️ 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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.66

Splicing

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

Publications

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2-182168293-GAAA-GAAAAAAA

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