14-29594820-T-C

Variant names:

• chr14-29594820-T-C
• rs3783297
• NM_002742.3:c.2434+2671A>G

Variant summary

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

The NM_002742.3(PRKD1):​c.2434+2671A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,912 control chromosomes in the GnomAD database, including 17,135 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 0.45 (17135 hom., cov: 31)
• Consequence: PRKD1 NM_002742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 5 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

LOC124903297 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD1	NM_002742.3	c.2434+2671A>G		intron_variant	Intron 16 of 17	ENST00000331968.11	NP_002733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD1	ENST00000331968.11	c.2434+2671A>G		intron_variant	Intron 16 of 17	1	NM_002742.3	ENSP00000333568.6

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68433 AN: 151792 Hom.: 17084 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.451 AC: 68552 AN: 151912 Hom.: 17135 Cov.: 31 AF XY: 0.447 AC XY: 33177 AN XY: 74222

African (AFR) AF: 0.686 AC: 28432 AN: 41422

American (AMR) AF: 0.385 AC: 5872 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1580 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1826 AN: 4812

European-Finnish (FIN) AF: 0.353 AC: 3720 AN: 10538

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.363 AC: 24696 AN: 67948

Other (OTH) AF: 0.397 AC: 839 AN: 2112

Alfa AF: 0.376 Hom.: 18888

Bravo AF: 0.462

Asia WGS AF: 0.365 AC: 1269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.77
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3783297; hg19: chr14-30064026;