rs225918

Variant names:

• chr14-29974448-G-A
• rs225918
• ENST00000549503.1:c.33+73262C>T

Variant summary

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

The ENST00000549503.1(PRKD1):​c.33+73262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,942 control chromosomes in the GnomAD database, including 35,865 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 0.67 (35865 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• 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
• congenital heart disease

  Inheritance: AD, AR Classification: LIMITED Submitted by: ClinGen

ENSG00000248975 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000549503.1	TSL:3	c.33+73262C>T		intron	N/A	ENSP00000446866.1	F8VZ98
	ENSG00000248975	ENST00000548124.1	TSL:3	n.106+5701C>T		intron	N/A
	ENSG00000248975	ENST00000549360.1	TSL:3	n.204-1215C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101550 AN: 151824 Hom.: 35860 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.669 AC: 101581 AN: 151942 Hom.: 35865 Cov.: 32 AF XY: 0.673 AC XY: 50030 AN XY: 74298

African (AFR) AF: 0.420 AC: 17371 AN: 41386

American (AMR) AF: 0.738 AC: 11263 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2558 AN: 3464

East Asian (EAS) AF: 0.763 AC: 3936 AN: 5158

South Asian (SAS) AF: 0.731 AC: 3523 AN: 4818

European-Finnish (FIN) AF: 0.822 AC: 8701 AN: 10584

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.767 AC: 52095 AN: 67952

Other (OTH) AF: 0.669 AC: 1411 AN: 2108

Alfa AF: 0.741 Hom.: 21098

Bravo AF: 0.652

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.53
PhyloP100		0.33

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs225918;

hg19: chr14-30443654;