14-30019105-C-T

Variant names:

• chr14-30019105-C-T
• rs226001
• ENST00000549503.1:c.33+28605G>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+28605G>A 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 152,004 control chromosomes in the GnomAD database, including 5,464 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 (5464 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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+28605G>A		intron	N/A	ENSP00000446866.1
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-38838G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40196 AN: 151886 Hom.: 5463 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.265 AC: 40222 AN: 152004 Hom.: 5464 Cov.: 32 AF XY: 0.266 AC XY: 19775 AN XY: 74282

African (AFR) AF: 0.262 AC: 10858 AN: 41460

American (AMR) AF: 0.265 AC: 4037 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2210 AN: 5154

South Asian (SAS) AF: 0.309 AC: 1491 AN: 4818

European-Finnish (FIN) AF: 0.305 AC: 3218 AN: 10554

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16550 AN: 67970

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.253 Hom.: 701

Bravo AF: 0.264

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.34
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs226001; hg19: chr14-30488311;