1-148967799-G-A

Position:

• chr1-148967799-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 8P and 2B. PVS1 BP6_Moderate

The NM_001395426.1(PDE4DIP):​c.1877G>A​(p.Trp626Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4DIP NM_001395426.1 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.59

Genes affected

PDE4DIP (HGNC:15580): (phosphodiesterase 4D interacting protein) The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 1-148967799-G-A is Benign according to our data. Variant chr1-148967799-G-A is described in ClinVar as [Benign]. Clinvar id is 2791670.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4DIP	NM_001395426.1	c.1877G>A	p.Trp626Ter	stop_gained	16/47	ENST00000695795.1	NP_001382355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4DIP	ENST00000695795.1	c.1877G>A	p.Trp626Ter	stop_gained	16/47		NM_001395426.1	ENSP00000512175

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1649 AN: 108500 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00522

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00987

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00667

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0521

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0115

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00777 AC: 6709 AN: 862984 Hom.: 0 Cov.: 14 AF XY: 0.00715 AC XY: 3218 AN XY: 450378

Gnomad4 AFR exome AF: 0.00729

Gnomad4 AMR exome AF: 0.000310

Gnomad4 ASJ exome AF: 0.00296

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.000897

Gnomad4 FIN exome AF: 0.00111

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.00687

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0152 AC: 1653 AN: 108578 Hom.: 0 Cov.: 27 AF XY: 0.0152 AC XY: 819 AN XY: 53774

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00987

Gnomad4 EAS AF: 0.000396

Gnomad4 SAS AF: 0.00692

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0115

Alfa AF: 0.289 Hom.: 661

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	38
DANN	Uncertain	1.0
Vest4		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1698683; hg19: chr1-144916676; COSMIC: COSV57717521; COSMIC: COSV57717521;