5-58969546-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001104631.2(PDE4D):c.*5118T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,094 control chromosomes in the GnomAD database, including 2,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2098 hom., cov: 32)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: PDE4D NM_001104631.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.464

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-58969546-A-C is Benign according to our data. Variant chr5-58969546-A-C is described in ClinVar as [Benign]. Clinvar id is 353914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.*5118T>G		3_prime_UTR_variant	15/15	ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.*5118T>G		3_prime_UTR_variant	15/15	1	NM_001104631.2
PDE4D	ENST00000507116.6	c.*5118T>G		3_prime_UTR_variant	15/15	1		P4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24441 AN: 151956 Hom.: 2097 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.300 AC: 6 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.278

GnomAD4 genome AF: 0.161 AC: 24463 AN: 152074 Hom.: 2098 Cov.: 32 AF XY: 0.164 AC XY: 12209 AN XY: 74320

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.142

Alfa AF: 0.152 Hom.: 2443

Bravo AF: 0.157

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acrodysostosis 2 with or without hormone resistance Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.8
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11959349; hg19: chr5-58265373;