rs62019510

Variant names:

• chr15-85113889-A-C
• rs62019510
• NM_002605.3:c.1202A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-85113889-A-C
• chr15-85113889-A-G
• chr15-85113889-A-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8A	NM_002605.3	c.1202A>C	p.Asn401Thr	missense_variant	Exon 14 of 22	ENST00000394553.6	NP_002596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8A	ENST00000394553.6	c.1202A>C	p.Asn401Thr	missense_variant	Exon 14 of 22	1	NM_002605.3	ENSP00000378056.1

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

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33398

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44504

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26080

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39684

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85992

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53408

Gnomad4 NFE exome AF: 0.00000270 AC: 3 AN: 1110870

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;.;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	M;.;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.071	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.82	P;.;P;D
Vest4		0.73
MutPred		0.36		Gain of helix (P = 0.0117);.;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

LitVar

Other links and lift over

dbSNP: rs62019510; hg19: chr15-85657120;