14-30117690-C-T

Variant names:

• chr14-30117690-C-T
• rs225858
• ENST00000549503.1:c.-45-69903G>A

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-45-69903G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,052 control chromosomes in the GnomAD database, including 63,525 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 0.91 (63525 hom., cov: 30)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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.-45-69903G>A		intron	N/A	ENSP00000446866.1	F8VZ98
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-137423G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138849 AN: 151934 Hom.: 63495 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.914 AC: 138932 AN: 152052 Hom.: 63525 Cov.: 30 AF XY: 0.912 AC XY: 67790 AN XY: 74320

African (AFR) AF: 0.888 AC: 36832 AN: 41462

American (AMR) AF: 0.937 AC: 14301 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3246 AN: 3468

East Asian (EAS) AF: 0.974 AC: 5027 AN: 5162

South Asian (SAS) AF: 0.968 AC: 4661 AN: 4816

European-Finnish (FIN) AF: 0.856 AC: 9042 AN: 10562

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62782 AN: 68000

Other (OTH) AF: 0.916 AC: 1930 AN: 2108

Alfa AF: 0.917 Hom.: 13318

Bravo AF: 0.918

Asia WGS AF: 0.967 AC: 3364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.53
DANN	Benign	0.32
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs225858;

hg19: chr14-30586896;