14-30158984-C-G

Variant names:

• chr14-30158984-C-G
• rs10483385
• ENST00000549503.1:c.-46+32315G>C

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-46+32315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,162 control chromosomes in the GnomAD database, including 87 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 0.026 (87 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• 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

ENSG00000248975 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 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.-46+32315G>C		intron_variant	Intron 2 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.84+137950G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3904 AN: 152044 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00374

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0192

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

GnomAD4 genome AF: 0.0257 AC: 3917 AN: 152162 Hom.: 87 Cov.: 32 AF XY: 0.0245 AC XY: 1826 AN XY: 74380

African (AFR) AF: 0.0601 AC: 2495 AN: 41528

American (AMR) AF: 0.0210 AC: 321 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4812

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0143 AC: 972 AN: 67992

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.0179 Hom.: 8

Bravo AF: 0.0285

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.33
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs10483385; hg19: chr14-30628190;