14-30020417-A-G

Variant names:

• chr14-30020417-A-G
• rs718545
• ENST00000549503.1:c.33+27293T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000549503.1(PRKD1):​c.33+27293T>C variant causes a intron change. The variant allele was found at a frequency of 0.088 in 152,240 control chromosomes in the GnomAD database, including 929 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 0.088 (929 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 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+27293T>C		intron_variant	Intron 3 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-40150T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13405 AN: 152122 Hom.: 929 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0880 AC: 13400 AN: 152240 Hom.: 929 Cov.: 32 AF XY: 0.0948 AC XY: 7058 AN XY: 74442

African (AFR) AF: 0.0206 AC: 856 AN: 41566

American (AMR) AF: 0.118 AC: 1807 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3466

East Asian (EAS) AF: 0.339 AC: 1753 AN: 5178

South Asian (SAS) AF: 0.185 AC: 893 AN: 4828

European-Finnish (FIN) AF: 0.137 AC: 1456 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0904 AC: 6146 AN: 67986

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0898 Hom.: 2250

Bravo AF: 0.0842

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.82
PhyloP100		5.8

Splicing

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

Other links and lift over

dbSNP: rs718545; hg19: chr14-30489623;