5-58969423-A-G

Position:

• chr5-58969423-A-G

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.*5241T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 152,266 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (590 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: PDE4D NM_001104631.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

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=-0.89).
• BP6: Variant 5-58969423-A-G is Benign according to our data. Variant chr5-58969423-A-G is described in ClinVar as [Benign]. Clinvar id is 353911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.*5241T>C		3_prime_UTR_variant	15/15	ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.*5241T>C		3_prime_UTR_variant	15/15	1	NM_001104631.2
PDE4D	ENST00000507116.6	c.*5241T>C		3_prime_UTR_variant	15/15	1		P4

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11112 AN: 152108 Hom.: 589 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.0709

GnomAD4 exome AF: 0.0500 AC: 2 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0731 AC: 11122 AN: 152226 Hom.: 590 Cov.: 32 AF XY: 0.0746 AC XY: 5553 AN XY: 74420

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0806 Hom.: 181

Bravo AF: 0.0750

Asia WGS AF: 0.0930 AC: 323 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 13, 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	-0.89
CADD	Benign	2.5
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11950495; hg19: chr5-58265250;