14-30137220-T-G

Variant names:

• chr14-30137220-T-G
• rs8019932
• ENST00000549503.1:c.-46+54079A>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+54079A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,968 control chromosomes in the GnomAD database, including 11,231 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 0.37 (11231 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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
• congenital heart disease

  Inheritance: AR, AD 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 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.-46+54079A>C		intron	N/A	ENSP00000446866.1
	ENSG00000248975	ENST00000549360.1	TSL:3	n.85-156953A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55805 AN: 151850 Hom.: 11228 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.00541

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.367 AC: 55835 AN: 151968 Hom.: 11231 Cov.: 32 AF XY: 0.363 AC XY: 26927 AN XY: 74266

African (AFR) AF: 0.520 AC: 21535 AN: 41414

American (AMR) AF: 0.375 AC: 5736 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3468

East Asian (EAS) AF: 0.00562 AC: 29 AN: 5164

South Asian (SAS) AF: 0.177 AC: 854 AN: 4824

European-Finnish (FIN) AF: 0.327 AC: 3451 AN: 10564

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22053 AN: 67950

Other (OTH) AF: 0.342 AC: 719 AN: 2104

Alfa AF: 0.357 Hom.: 1492

Bravo AF: 0.376

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs8019932; hg19: chr14-30606426;