5-59801097-C-T

Variant names:

• chr5-59801097-C-T
• rs2963826
• NM_001104631.2:c.455+92071G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001104631.2(PDE4D):​c.455+92071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,906 control chromosomes in the GnomAD database, including 10,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10361 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 10 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001104631.2	MANE Select	c.455+92071G>A		intron	N/A	NP_001098101.1	A0A140VJR0
	PDE4D	NM_001165899.2		c.272+187391G>A		intron	N/A	NP_001159371.1	Q08499-11
	PDE4D	NM_001364599.1		c.272+187391G>A		intron	N/A	NP_001351528.1	Q08499-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	ENST00000340635.11	TSL:1 MANE Select	c.455+92071G>A		intron	N/A	ENSP00000345502.6	Q08499-1
	PDE4D	ENST00000502484.6	TSL:1	c.272+187391G>A		intron	N/A	ENSP00000423094.2	Q08499-11
	PDE4D	ENST00000405053.7	TSL:5	n.118+92071G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53499 AN: 151788 Hom.: 10369 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.352 AC: 53503 AN: 151906 Hom.: 10361 Cov.: 32 AF XY: 0.354 AC XY: 26280 AN XY: 74230

African (AFR) AF: 0.213 AC: 8831 AN: 41418

American (AMR) AF: 0.335 AC: 5111 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3470

East Asian (EAS) AF: 0.179 AC: 926 AN: 5166

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4828

European-Finnish (FIN) AF: 0.503 AC: 5282 AN: 10510

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29149 AN: 67960

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.387 Hom.: 20608

Bravo AF: 0.333

Asia WGS AF: 0.247 AC: 861 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2963826; hg19: chr5-59096923; COSMIC: COSV61426437;