chr14-29803103-T-G

Variant names:

• chr14-29803103-T-G
• rs10144903
• NM_002742.3:c.265-77429A>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.265-77429A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,058 control chromosomes in the GnomAD database, including 3,891 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 0.22 (3891 hom., cov: 32)
• Consequence: PRKD1 NM_002742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD1	NM_002742.3	c.265-77429A>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.265-77429A>C		intron_variant	Intron 1 of 17	1	NM_002742.3	ENSP00000333568.6
PRKD1	ENST00000415220.6	c.265-77429A>C		intron_variant	Intron 1 of 18	5		ENSP00000390535.2
PRKD1	ENST00000549503.1	c.34-77429A>C		intron_variant	Intron 3 of 5	3		ENSP00000446866.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32951 AN: 151938 Hom.: 3867 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.217 AC: 33025 AN: 152058 Hom.: 3891 Cov.: 32 AF XY: 0.215 AC XY: 15973 AN XY: 74308

African (AFR) AF: 0.293 AC: 12133 AN: 41438

American (AMR) AF: 0.146 AC: 2236 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.0870 AC: 449 AN: 5160

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10566

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13662 AN: 67992

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.201 Hom.: 13233

Bravo AF: 0.212

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.058
DANN	Benign	0.44
PhyloP100		-2.1
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: rs10144903; hg19: chr14-30272309;