rs1440983

Variant names:

• chr14-30024055-G-A
• rs1440983
• ENST00000549503.1:c.33+23655C>T

Variant summary

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

The ENST00000549503.1(PRKD1):​c.33+23655C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 152,106 control chromosomes in the GnomAD database, including 1,318 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 0.096 (1318 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 7 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 = 0.232 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+23655C>T		intron_variant	Intron 3 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-43788C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14552 AN: 151990 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0901

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0959 AC: 14591 AN: 152106 Hom.: 1318 Cov.: 32 AF XY: 0.0945 AC XY: 7026 AN XY: 74364

African (AFR) AF: 0.236 AC: 9787 AN: 41466

American (AMR) AF: 0.0617 AC: 944 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5166

South Asian (SAS) AF: 0.0892 AC: 429 AN: 4812

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2777 AN: 67998

Other (OTH) AF: 0.0890 AC: 187 AN: 2102

Alfa AF: 0.0963 Hom.: 209

Bravo AF: 0.106

Asia WGS AF: 0.0630 AC: 220 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	5.2
DANN	Benign	0.65
PhyloP100		-0.030

Splicing

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

Other links and lift over

dbSNP: rs1440983; hg19: chr14-30493261;