Variant 5-58989926-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001104631.2(PDE4D):c.1288-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,466,354 control chromosomes in the GnomAD database, including 85 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 59 hom. )

Consequence

PDE4D
NM_001104631.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D links:

PDE4D (HGNC:):

PDE4D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-58989926-G-GA is Benign according to our data. Variant chr5-58989926-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 235668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0154 (2323/151302) while in subpopulation AFR AF= 0.0339 (1399/41252). AF 95% confidence interval is 0.0324. There are 26 homozygotes in gnomad4. There are 1067 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2323 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2 linkuse as main transcript	c.1288-8dupT		splice_region_variant, intron_variant		ENST00000340635.11	NP_001098101.1	Q08499-1A0A140VJR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11 linkuse as main transcript	c.1288-8dupT		splice_region_variant, intron_variant		1	NM_001104631.2	ENSP00000345502.6		Q08499-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2323

AN:

151184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00883

Gnomad AMR

AF:

0.00514

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00918

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0102

GnomAD3 exomes

AF:

0.00759

AC:

1563

AN:

206014

Hom.:

AF XY:

0.00681

AC XY:

765

AN XY:

112412

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.000270

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000874

Gnomad FIN exome

AF:

0.00912

Gnomad NFE exome

AF:

0.00804

Gnomad OTH exome

AF:

0.00593

GnomAD4 exome

AF:

0.00855

AC:

11250

AN:

1315052

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

5431

AN XY:

659012

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.000297

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000981

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.00916

Gnomad4 OTH exome

AF:

0.00820

GnomAD4 genome

AF:

0.0154

AC:

2323

AN:

151302

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1067

AN XY:

73912

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.00514

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00918

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0101

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 01, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Acrodysostosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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