rs702531

Variant names:

• chr5-58971896-A-C
• rs702531
• NM_001104631.2:c.*2768T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-58971896-A-C
• chr5-58971896-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001104631.2(PDE4D):​c.*2768T>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 0.657 in 152,336 control chromosomes in the GnomAD database, including 32,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (32871 hom., cov: 31)
  • Exomes 𝑓: 0.65 (98 hom.)
• Consequence: PDE4D NM_001104631.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.47
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-58971896-A-C is Benign according to our data. Variant chr5-58971896-A-C is described in ClinVar as Benign. ClinVar VariationId is 353937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.681 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.*2768T>G		3_prime_UTR	Exon 15 of 15	NP_001098101.1	A0A140VJR0
	PDE4D	NM_001165899.2		c.*2768T>G		3_prime_UTR	Exon 17 of 17	NP_001159371.1	Q08499-11
	PDE4D	NM_001364599.1		c.*2768T>G		3_prime_UTR	Exon 17 of 17	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.*2768T>G		3_prime_UTR	Exon 15 of 15	ENSP00000345502.6	Q08499-1
	PDE4D	ENST00000507116.6	TSL:1	c.*2768T>G		3_prime_UTR	Exon 15 of 15	ENSP00000424852.1	Q08499-6
	PDE4D	ENST00000636120.1	TSL:5	c.*2768T>G		3_prime_UTR	Exon 15 of 15	ENSP00000490821.1	A0A1B0GW84

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99735 AN: 151780 Hom.: 32854 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.653 AC: 286 AN: 438 Hom.: 98 Cov.: 0 AF XY: 0.633 AC XY: 167 AN XY: 264

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.646 AC: 275 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.657 AC: 99793 AN: 151898 Hom.: 32871 Cov.: 31 AF XY: 0.654 AC XY: 48562 AN XY: 74208

African (AFR) AF: 0.603 AC: 24989 AN: 41438

American (AMR) AF: 0.692 AC: 10540 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2514 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3410 AN: 5154

South Asian (SAS) AF: 0.670 AC: 3229 AN: 4818

European-Finnish (FIN) AF: 0.613 AC: 6461 AN: 10546

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46335 AN: 67926

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.680 Hom.: 53083

Bravo AF: 0.665

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Acrodysostosis 2 with or without hormone resistance (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.6
DANN	Benign	0.84
PhyloP100		2.5
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: rs702531; hg19: chr5-58267723; COSMIC: COSV57717084; COSMIC: COSV57717084;