rs225830

Variant names:

• chr14-30071535-G-A
• rs225830
• ENST00000549503.1:c.-45-23748C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-30071535-G-A
• chr14-30071535-G-C

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-45-23748C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,040 control chromosomes in the GnomAD database, including 27,942 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 0.60 (27942 hom., cov: 33)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 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.-45-23748C>T		intron	N/A	ENSP00000446866.1	F8VZ98
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-91268C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91601 AN: 151924 Hom.: 27927 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.603 AC: 91667 AN: 152040 Hom.: 27942 Cov.: 33 AF XY: 0.606 AC XY: 45043 AN XY: 74302

African (AFR) AF: 0.568 AC: 23544 AN: 41462

American (AMR) AF: 0.695 AC: 10605 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4652 AN: 5176

South Asian (SAS) AF: 0.620 AC: 2989 AN: 4818

European-Finnish (FIN) AF: 0.637 AC: 6724 AN: 10554

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39323 AN: 67972

Other (OTH) AF: 0.585 AC: 1237 AN: 2114

Alfa AF: 0.496 Hom.: 1493

Bravo AF: 0.609

Asia WGS AF: 0.748 AC: 2600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.7
DANN	Benign	0.25
PhyloP100		1.2

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: rs225830;

hg19: chr14-30540741;