14-30056182-T-C

Variant names:

• chr14-30056182-T-C
• rs225942
• ENST00000549503.1:c.-45-8395A>G

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-45-8395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,490 control chromosomes in the GnomAD database, including 32,344 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 0.65 (32344 hom., cov: 31)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 2 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 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.-45-8395A>G		intron_variant	Intron 2 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-75915A>G		intron_variant	Intron 1 of 2	3
ENSG00000240201	ENST00000493565.1	n.*228T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98157 AN: 151370 Hom.: 32309 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.649 AC: 98250 AN: 151490 Hom.: 32344 Cov.: 31 AF XY: 0.651 AC XY: 48189 AN XY: 73992

African (AFR) AF: 0.717 AC: 29680 AN: 41400

American (AMR) AF: 0.724 AC: 10983 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1954 AN: 3464

East Asian (EAS) AF: 0.899 AC: 4617 AN: 5136

South Asian (SAS) AF: 0.622 AC: 2980 AN: 4792

European-Finnish (FIN) AF: 0.636 AC: 6669 AN: 10480

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.582 AC: 39393 AN: 67738

Other (OTH) AF: 0.625 AC: 1318 AN: 2110

Alfa AF: 0.618 Hom.: 3620

Bravo AF: 0.663

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.2
DANN	Benign	0.90
PhyloP100		-0.035

Splicing

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

Other links and lift over

dbSNP: rs225942; hg19: chr14-30525388;