chr14-29611730-A-G

Variant names:

• chr14-29611730-A-G
• rs8021268
• NM_002742.3:c.1906-11913T>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.1906-11913T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 139,474 control chromosomes in the GnomAD database, including 499 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 0.057 (499 hom., cov: 29)
• Consequence: PRKD1 NM_002742.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002742.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	NM_002742.3	MANE Select	c.1906-11913T>C		intron	N/A	NP_002733.2
	PRKD1	NM_001330069.2		c.1930-11913T>C		intron	N/A	NP_001316998.1
	PRKD1	NM_001348390.1		c.1642-11913T>C		intron	N/A	NP_001335319.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000331968.11	TSL:1 MANE Select	c.1906-11913T>C		intron	N/A	ENSP00000333568.6
	PRKD1	ENST00000415220.6	TSL:5	c.1930-11913T>C		intron	N/A	ENSP00000390535.2
	PRKD1	ENST00000616995.5	TSL:5	n.1677-11913T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 7954 AN: 139382 Hom.: 498 Cov.: 29

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0401

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.00389

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0428

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

GnomAD4 genome AF: 0.0571 AC: 7957 AN: 139474 Hom.: 499 Cov.: 29 AF XY: 0.0597 AC XY: 4011 AN XY: 67180

African (AFR) AF: 0.139 AC: 5425 AN: 39132

American (AMR) AF: 0.0582 AC: 748 AN: 12850

Ashkenazi Jewish (ASJ) AF: 0.00389 AC: 13 AN: 3342

East Asian (EAS) AF: 0.00136 AC: 6 AN: 4416

South Asian (SAS) AF: 0.191 AC: 796 AN: 4166

European-Finnish (FIN) AF: 0.0117 AC: 98 AN: 8404

Middle Eastern (MID) AF: 0.00388 AC: 1 AN: 258

European-Non Finnish (NFE) AF: 0.0118 AC: 758 AN: 64214

Other (OTH) AF: 0.0423 AC: 78 AN: 1844

Alfa AF: 0.0246 Hom.: 190

Bravo AF: 0.0565

Asia WGS AF: 0.0850 AC: 294 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.74
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: rs8021268; hg19: chr14-30080936;