rs1158219

chr2-37319677-T-A

Variant summary

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

The NM_005813.6(PRKD3):c.-655-2498A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,450 control chromosomes in the GnomAD database, including 8,853 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 0.33 (8853 hom., cov: 31)
• Consequence: PRKD3 NM_005813.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

Genes affected

PRKD3 (HGNC:9408): (protein kinase D3) This gene belongs to the multigene protein kinase D family of serine/threonine kinases, which bind diacylglycerol and phorbol esters. Members of this family are characterized by an N-terminal regulatory domain comprised of a tandem repeat of cysteine-rich zinc-finger motifs and a pleckstrin domain. The C-terminal region contains the catalytic domain and is distantly related to calcium-regulated kinases. Catalytic activity of this enzyme promotes its nuclear localization. This protein has been implicated in a variety of functions including negative regulation of human airway epithelial barrier formation, growth regulation of breast and prostate cancer cells, and vesicle trafficking. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKD3	NM_005813.6	c.-655-2498A>T		intron_variant		ENST00000234179.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKD3	ENST00000234179.8	c.-655-2498A>T		intron_variant		1	NM_005813.6	P1
PRKD3	ENST00000443187.1	c.-25+5004A>T		intron_variant		4
PRKD3	ENST00000477132.1	n.174-2498A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49602 AN: 151332 Hom.: 8853 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49620 AN: 151450 Hom.: 8853 Cov.: 31 AF XY: 0.333 AC XY: 24646 AN XY: 73974

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.352

Alfa AF: 0.341 Hom.: 1195

Bravo AF: 0.314

Asia WGS AF: 0.354 AC: 1227 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1158219; hg19: chr2-37546820;