5-58989926-GA-GAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

acrodysostosis 2 with or without hormone resistance
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
acrodysostosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
acrodysostosis with multiple hormone resistance
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
chromosome 5q12 deletion syndrome
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

PDE4D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2323 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2 link	c.1288-8dupT		splice_region_variant, intron_variant	Intron 9 of 14	ENST00000340635.11	NP_001098101.1	Q08499-1A0A140VJR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11 link	c.1288-8_1288-7insT		splice_region_variant, intron_variant	Intron 9 of 14	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

GnomAD2 exomes

AF:

0.00759

AC:

1563

AN:

206014

AF XY:

0.00681

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 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

African (AFR)

AF:

0.0297

AC:

855

AN:

28746

American (AMR)

AF:

0.00463

AC:

165

AN:

35670

Ashkenazi Jewish (ASJ)

AF:

0.000297

AC:

AN:

23572

East Asian (EAS)

AF:

0.00

AC:

AN:

38176

South Asian (SAS)

AF:

0.000981

AC:

AN:

77442

European-Finnish (FIN)

AF:

0.0100

AC:

526

AN:

52556

Middle Eastern (MID)

AF:

0.00489

AC:

AN:

5316

European-Non Finnish (NFE)

AF:

0.00916

AC:

9144

AN:

998580

Other (OTH)

AF:

0.00820

AC:

451

AN:

54994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

471

943

1414

1886

2357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0154

AC:

2323

AN:

151302

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1067

AN XY:

73912

show subpopulations

African (AFR)

AF:

0.0339

AC:

1399

AN:

41252

American (AMR)

AF:

0.00514

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00126

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00918

AC:

AN:

10346

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

712

AN:

67820

Other (OTH)

AF:

0.0101

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

112

224

335

447

559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Feb 01, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Acrodysostosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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5-58989926-GA-GAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over