Variant 2-182201710-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363871.4(PDE1A):c.982A>G(p.Asn328Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,607,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PDE1A
NM_001363871.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22583902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1A	NM_001363871.4 linkuse as main transcript	c.982A>G	p.Asn328Asp	missense_variant	9/15	ENST00000409365.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1A	ENST00000409365.6 linkuse as main transcript	c.982A>G	p.Asn328Asp	missense_variant	9/15	5	NM_001363871.4	A1	P54750-6

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151152

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1456684

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724434

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73712

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.1030A>G (p.N344D) alteration is located in exon 9 (coding exon 9) of the PDE1A gene. This alteration results from a A to G substitution at nucleotide position 1030, causing the asparagine (N) at amino acid position 344 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

-0.084

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.92

L;.;.;.;L

MutationTaster

Benign

0.97

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.035

D;T;D;T;T

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

0.0030

B;.;B;B;B

Vest4

0.28

MutPred

0.50

Gain of ubiquitination at K340 (P = 0.0797);.;.;.;Gain of ubiquitination at K340 (P = 0.0797);

MVP

0.49

MPC

0.37

ClinPred

0.46

GERP RS

5.1

Varity_R

0.24

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over