chr5-59039095-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000515011.5(PDE4D):n.421C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,453,192 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 90 hom. )

Consequence

PDE4D
ENST00000515011.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.47

Publications

6 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:

ENSG00000247345 (HGNC:58182):

ENSG00000247345 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-59039095-G-T is Benign according to our data. Variant chr5-59039095-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1293 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515011.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDE4D	NM_001104631.2	MANE Select	c.809-124C>A		intron	N/A	NP_001098101.1
PDE4D	NM_001197222.2		c.13C>A	p.Pro5Thr	missense	Exon 1 of 10	NP_001184151.1
PDE4D	NM_001197221.2		c.-136C>A		5_prime_UTR	Exon 1 of 11	NP_001184150.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDE4D	ENST00000515011.5	TSL:1	n.421C>A	non_coding_transcript_exon	Exon 1 of 10
PDE4D	ENST00000358923.10	TSL:1	c.-136C>A	5_prime_UTR	Exon 1 of 11	ENSP00000351800.6
PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.809-124C>A	intron	N/A	ENSP00000345502.6

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1293

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00970

AC:

650

AN:

67008

AF XY:

0.0104

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.00551

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.00843

GnomAD4 exome

AF:

0.0105

AC:

13700

AN:

1300878

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

6787

AN XY:

634404

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

27832

American (AMR)

AF:

0.00458

AC:

113

AN:

24654

Ashkenazi Jewish (ASJ)

AF:

0.00333

AC:

AN:

19802

East Asian (EAS)

AF:

0.00

AC:

AN:

31306

South Asian (SAS)

AF:

0.00236

AC:

154

AN:

65196

European-Finnish (FIN)

AF:

0.0180

AC:

718

AN:

39794

Middle Eastern (MID)

AF:

0.000383

AC:

AN:

5222

European-Non Finnish (NFE)

AF:

0.0119

AC:

12251

AN:

1033168

Other (OTH)

AF:

0.00670

AC:

361

AN:

53904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

720

1440

2161

2881

3601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

436

872

1308

1744

2180

<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

AF:

0.00849

AC:

1293

AN:

152314

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41584

American (AMR)

AF:

0.00418

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00310

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0189

AC:

201

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0135

AC:

918

AN:

68026

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00661

Asia WGS

AF:

0.000577

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 28, 2017

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDE4D: BS1, BS2

PDE4D-related disorder

Benign:1

Jun 13, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.5

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over