2-37319677-T-A

Variant names:

• chr2-37319677-T-A
• rs1158219
• NM_005813.6:c.-655-2498A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005813.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD3	NM_005813.6	MANE Select	c.-655-2498A>T		intron	N/A	NP_005804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD3	ENST00000234179.8	TSL:1 MANE Select	c.-655-2498A>T		intron	N/A	ENSP00000234179.2
	PRKD3	ENST00000933386.1		c.-655-2498A>T		intron	N/A	ENSP00000603445.1
	PRKD3	ENST00000933388.1		c.-655-2498A>T		intron	N/A	ENSP00000603447.1

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

African (AFR) AF: 0.190 AC: 7840 AN: 41362

American (AMR) AF: 0.317 AC: 4826 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1614 AN: 3438

East Asian (EAS) AF: 0.427 AC: 2194 AN: 5134

South Asian (SAS) AF: 0.248 AC: 1187 AN: 4782

European-Finnish (FIN) AF: 0.491 AC: 5120 AN: 10434

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25654 AN: 67790

Other (OTH) AF: 0.352 AC: 736 AN: 2088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1158219; hg19: chr2-37546820;