5-59041654-T-G

Variant names:

• chr5-59041654-T-G
• rs1353747
• NM_001104631.2:c.809-2683A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001104631.2(PDE4D):​c.809-2683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,226 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (508 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990
• Publications: 70 publications found

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

ENSG00000247345 (HGNC:58182):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-59041654-T-G is Benign according to our data. Variant chr5-59041654-T-G is described in ClinVar as Benign. ClinVar VariationId is 225788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104631.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001104631.2	MANE Select	c.809-2683A>C		intron	N/A	NP_001098101.1
	PDE4D	NM_001165899.2		c.626-2683A>C		intron	N/A	NP_001159371.1
	PDE4D	NM_001364599.1		c.626-2683A>C		intron	N/A	NP_001351528.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.809-2683A>C		intron	N/A	ENSP00000345502.6
	PDE4D	ENST00000502484.6	TSL:1	c.626-2683A>C		intron	N/A	ENSP00000423094.2
	PDE4D	ENST00000507116.6	TSL:1	c.617-2683A>C		intron	N/A	ENSP00000424852.1

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10482 AN: 152108 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.0770

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0689 AC: 10481 AN: 152226 Hom.: 508 Cov.: 32 AF XY: 0.0682 AC XY: 5078 AN XY: 74422

African (AFR) AF: 0.0187 AC: 777 AN: 41556

American (AMR) AF: 0.107 AC: 1629 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4830

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6589 AN: 68000

Other (OTH) AF: 0.0762 AC: 161 AN: 2112

Alfa AF: 0.0838 Hom.: 1158

Bravo AF: 0.0698

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.79
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1353747; hg19: chr5-58337481;