chr15-84982239-T-G

Variant names:

• chr15-84982239-T-G
• NM_002605.3:c.77T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002605.3(PDE8A):​c.77T>G​(p.Leu26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE8A NM_002605.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07810357).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	NM_002605.3	MANE Select	c.77T>G	p.Leu26Arg	missense	Exon 1 of 22	NP_002596.1	O60658-1
	PDE8A	NM_173454.1		c.77T>G	p.Leu26Arg	missense	Exon 1 of 21	NP_775656.1	O60658-2
	PDE8A	NM_001243137.2		c.-31+1554T>G		intron	N/A	NP_001230066.1	O60658-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8A	ENST00000394553.6	TSL:1 MANE Select	c.77T>G	p.Leu26Arg	missense	Exon 1 of 22	ENSP00000378056.1	O60658-1
	PDE8A	ENST00000310298.8	TSL:1	c.77T>G	p.Leu26Arg	missense	Exon 2 of 23	ENSP00000311453.4	O60658-1
	PDE8A	ENST00000339708.9	TSL:1	c.77T>G	p.Leu26Arg	missense	Exon 1 of 21	ENSP00000340679.5	O60658-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.2
DANN	Benign	0.65
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.069
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.080
Sift	Benign	0.086	T
Sift4G	Benign	0.83	T
Polyphen		0.022	B
Vest4		0.10
MutPred		0.11		Gain of solvent accessibility (P = 0.0062)
MVP		0.27
MPC		0.27
ClinPred		0.17	T
GERP RS		-2.5
PromoterAI		-0.00070	Neutral
Varity_R		0.082
gMVP		0.17

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

Other links and lift over

hg19: chr15-85525470;