ENST00000549503.1:c.33+1804G>A

Variant names:

• chr14-30045906-C-T
• rs11847697
• ENST00000549503.1:c.33+1804G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549503.1(PRKD1):​c.33+1804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,970 control chromosomes in the GnomAD database, including 2,634 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 0.13 (2634 hom., cov: 30)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 152 publications found

Genes affected

PRKD1 (HGNC:9407): (protein kinase D1) The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]

PRKD1 Gene-Disease associations (from GenCC):

• congenital heart defects and ectodermal dysplasia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart defects, multiple types

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000248975 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549503.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000549503.1	TSL:3	c.33+1804G>A		intron	N/A	ENSP00000446866.1
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-65639G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19447 AN: 151852 Hom.: 2633 Cov.: 30

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.128 AC: 19470 AN: 151970 Hom.: 2634 Cov.: 30 AF XY: 0.126 AC XY: 9361 AN XY: 74276

African (AFR) AF: 0.344 AC: 14252 AN: 41406

American (AMR) AF: 0.0710 AC: 1084 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5148

South Asian (SAS) AF: 0.0894 AC: 430 AN: 4810

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10580

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 2995 AN: 67978

Other (OTH) AF: 0.112 AC: 236 AN: 2106

Alfa AF: 0.0668 Hom.: 2680

Bravo AF: 0.142

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs11847697; hg19: chr14-30515112;