chr14-30056395-C-T

Variant names:

• chr14-30056395-C-T
• rs41449149
• ENST00000549503.1:c.-45-8608G>A

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-45-8608G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,052 control chromosomes in the GnomAD database, including 302 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 0.053 (302 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0998 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.-45-8608G>A		intron_variant	Intron 2 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-76128G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8040 AN: 151932 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0670

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

GnomAD4 genome AF: 0.0529 AC: 8042 AN: 152052 Hom.: 302 Cov.: 32 AF XY: 0.0559 AC XY: 4152 AN XY: 74332

African (AFR) AF: 0.0133 AC: 552 AN: 41500

American (AMR) AF: 0.0730 AC: 1113 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.107 AC: 551 AN: 5140

South Asian (SAS) AF: 0.0752 AC: 363 AN: 4824

European-Finnish (FIN) AF: 0.0861 AC: 911 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3870 AN: 67962

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0508 Hom.: 58

Bravo AF: 0.0520

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.69
PhyloP100		-0.054

Splicing

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

Other links and lift over

dbSNP: rs41449149; hg19: chr14-30525601;