rs2292399

Positions:

• chr8-49074671-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000303202.8(PPDPFL):​c.*140A>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 0.362 in 1,506,684 control chromosomes in the GnomAD database, including 102,531 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 0.31 (8228 hom., cov: 32)
  • Exomes 𝑓: 0.37 (94303 hom.)
• Consequence: PPDPFL ENST00000303202.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

Genes affected

PPDPFL (HGNC:31745): (pancreatic progenitor cell differentiation and proliferation factor like) Predicted to be involved in cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPDPFL	NM_001256597.2	c.233+338A>G		intron_variant		ENST00000522267.6
PPDPFL	NM_001256598.2	c.*140A>G		3_prime_UTR_variant	5/5
PPDPFL	NM_001007176.5	c.233+338A>G		intron_variant
PPDPFL	NM_001256596.1	c.233+338A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPDPFL	ENST00000303202.8	c.*140A>G		3_prime_UTR_variant	5/5	1
PPDPFL	ENST00000522267.6	c.233+338A>G		intron_variant		2	NM_001256597.2
PPDPFL	ENST00000399653.8	c.233+338A>G		intron_variant		1		P1
PPDPFL	ENST00000517663.5	c.233+338A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47542 AN: 151962 Hom.: 8227 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.368 AC: 497921 AN: 1354606 Hom.: 94303 Cov.: 33 AF XY: 0.363 AC XY: 241524 AN XY: 665198

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.349

GnomAD4 genome AF: 0.313 AC: 47558 AN: 152078 Hom.: 8228 Cov.: 32 AF XY: 0.314 AC XY: 23358 AN XY: 74328

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.332

Alfa AF: 0.367 Hom.: 10305

Bravo AF: 0.298

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.69

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: rs2292399; hg19: chr8-49987230;