rs225848

Variant names:

• chr14-30125451-G-A
• rs225848
• ENST00000549503.1:c.-46+65848C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-30125451-G-A
• chr14-30125451-G-C
• chr14-30125451-G-T

Variant summary

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

The ENST00000549503.1(PRKD1):​c.-46+65848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,224 control chromosomes in the GnomAD database, including 63,947 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 0.92 (63947 hom., cov: 32)
• Consequence: PRKD1 ENST00000549503.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• 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 (EAS) allele frequency at 95% confidence interval = 0.951 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.-46+65848C>T		intron_variant	Intron 2 of 5	3		ENSP00000446866.1
ENSG00000248975	ENST00000549360.1	n.85-145184C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139386 AN: 152106 Hom.: 63909 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.969

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.916 AC: 139480 AN: 152224 Hom.: 63947 Cov.: 32 AF XY: 0.915 AC XY: 68047 AN XY: 74404

African (AFR) AF: 0.897 AC: 37273 AN: 41544

American (AMR) AF: 0.937 AC: 14338 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5045 AN: 5182

South Asian (SAS) AF: 0.968 AC: 4677 AN: 4830

European-Finnish (FIN) AF: 0.856 AC: 9060 AN: 10580

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62788 AN: 68000

Other (OTH) AF: 0.917 AC: 1941 AN: 2116

Alfa AF: 0.925 Hom.: 123202

Bravo AF: 0.921

Asia WGS AF: 0.968 AC: 3368 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	15
DANN	Benign	0.43
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs225848; hg19: chr14-30594657;