rs62019510

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002605.3(PDE8A):​c.1202A>C​(p.Asn401Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PDE8A
NM_002605.3 missense

Scores

7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

0 publications found
Variant links:
Genes affected
PDE8A (HGNC:8793): (phosphodiesterase 8A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002605.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PDE8A
NM_002605.3
MANE Select
c.1202A>Cp.Asn401Thr
missense
Exon 14 of 22NP_002596.1
PDE8A
NM_173454.1
c.1064A>Cp.Asn355Thr
missense
Exon 13 of 21NP_775656.1
PDE8A
NM_001243137.2
c.986A>Cp.Asn329Thr
missense
Exon 14 of 22NP_001230066.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PDE8A
ENST00000394553.6
TSL:1 MANE Select
c.1202A>Cp.Asn401Thr
missense
Exon 14 of 22ENSP00000378056.1
PDE8A
ENST00000310298.8
TSL:1
c.1202A>Cp.Asn401Thr
missense
Exon 15 of 23ENSP00000311453.4
PDE8A
ENST00000339708.9
TSL:1
c.1064A>Cp.Asn355Thr
missense
Exon 13 of 21ENSP00000340679.5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460010
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726386
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33398
American (AMR)
AF:
0.00
AC:
0
AN:
44504
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85992
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1110870
Other (OTH)
AF:
0.00
AC:
0
AN:
60314
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T
Eigen
Benign
0.18
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.50
T
MetaSVM
Benign
-0.42
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
5.0
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.21
Sift
Benign
0.071
T
Sift4G
Benign
0.20
T
Polyphen
0.82
P
Vest4
0.73
MutPred
0.36
Gain of helix (P = 0.0117)
MVP
0.44
MPC
0.37
ClinPred
0.96
D
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
gMVP
0.43
Mutation Taster
=48/52
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs62019510; hg19: chr15-85657120; API