ENST00000549503.1:c.33+26554T>G

Variant names:

• chr14-30021156-A-C
• rs225998
• ENST00000549503.1:c.33+26554T>G

Variant summary

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

The ENST00000549503.1(PRKD1):​c.33+26554T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,044 control chromosomes in the GnomAD database, including 5,462 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 0.26 (5462 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD1	ENST00000549503.1	c.33+26554T>G		intron_variant	Intron 3 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-40889T>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40248 AN: 151926 Hom.: 5461 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.265 AC: 40272 AN: 152044 Hom.: 5462 Cov.: 32 AF XY: 0.267 AC XY: 19819 AN XY: 74328

African (AFR) AF: 0.262 AC: 10853 AN: 41478

American (AMR) AF: 0.266 AC: 4057 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1042 AN: 3460

East Asian (EAS) AF: 0.430 AC: 2220 AN: 5158

South Asian (SAS) AF: 0.314 AC: 1518 AN: 4828

European-Finnish (FIN) AF: 0.305 AC: 3228 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16543 AN: 67962

Other (OTH) AF: 0.291 AC: 614 AN: 2108

Alfa AF: 0.253 Hom.: 611

Bravo AF: 0.264

Asia WGS AF: 0.378 AC: 1311 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		0.056

Splicing

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

Other links and lift over

dbSNP: rs225998; hg19: chr14-30490362;