NM_002742.3:c.264+29843T>C

Variant names:

• chr14-29897406-A-G
• rs17096124
• NM_002742.3:c.264+29843T>C

Variant summary

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

The NM_002742.3(PRKD1):​c.264+29843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,222 control chromosomes in the GnomAD database, including 395 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 0.065 (395 hom., cov: 32)
• Consequence: PRKD1 NM_002742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD1	NM_002742.3	c.264+29843T>C		intron_variant	Intron 1 of 17	ENST00000331968.11	NP_002733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD1	ENST00000331968.11	c.264+29843T>C		intron_variant	Intron 1 of 17	1	NM_002742.3	ENSP00000333568.6
PRKD1	ENST00000415220.6	c.264+29843T>C		intron_variant	Intron 1 of 18	5		ENSP00000390535.2
PRKD1	ENST00000549503.1	c.33+150304T>C		intron_variant	Intron 3 of 5	3		ENSP00000446866.1

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9867 AN: 152106 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0691

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

GnomAD4 genome AF: 0.0649 AC: 9883 AN: 152222 Hom.: 395 Cov.: 32 AF XY: 0.0665 AC XY: 4953 AN XY: 74440

African (AFR) AF: 0.107 AC: 4425 AN: 41528

American (AMR) AF: 0.0479 AC: 733 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.0819 AC: 425 AN: 5190

South Asian (SAS) AF: 0.113 AC: 547 AN: 4826

European-Finnish (FIN) AF: 0.0360 AC: 382 AN: 10618

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2823 AN: 67986

Other (OTH) AF: 0.0712 AC: 150 AN: 2106

Alfa AF: 0.0537 Hom.: 38

Bravo AF: 0.0661

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.67
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: rs17096124; hg19: chr14-30366612;