rs1953722

Variant names:

• chr14-29761432-A-G
• rs1953722
• NM_002742.3:c.265-35758T>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.265-35758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,004 control chromosomes in the GnomAD database, including 7,998 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 0.32 (7998 hom., cov: 31)
• Consequence: PRKD1 NM_002742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD1	NM_002742.3	c.265-35758T>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.265-35758T>C		intron_variant	Intron 1 of 17	1	NM_002742.3	ENSP00000333568.6
PRKD1	ENST00000415220.6	c.265-35758T>C		intron_variant	Intron 1 of 18	5		ENSP00000390535.2
PRKD1	ENST00000549503.1	c.34-35758T>C		intron_variant	Intron 3 of 5	3		ENSP00000446866.1
PRKD1	ENST00000616995.5	n.35+9985T>C		intron_variant	Intron 1 of 17	5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47921 AN: 151886 Hom.: 7962 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.316 AC: 48019 AN: 152004 Hom.: 7998 Cov.: 31 AF XY: 0.316 AC XY: 23456 AN XY: 74300

African (AFR) AF: 0.407 AC: 16873 AN: 41450

American (AMR) AF: 0.328 AC: 5017 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 900 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5160

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4820

European-Finnish (FIN) AF: 0.237 AC: 2504 AN: 10574

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18595 AN: 67938

Other (OTH) AF: 0.308 AC: 650 AN: 2108

Alfa AF: 0.285 Hom.: 26972

Bravo AF: 0.321

Asia WGS AF: 0.324 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-0.64
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: rs1953722; hg19: chr14-30230638;