rs1057519635

Positions:

• chr14-29626508-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_002742.3(PRKD1):​c.1774G>A​(p.Gly592Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G592G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKD1 NM_002742.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.86

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981
• PP5: Variant 14-29626508-C-T is Pathogenic according to our data. Variant chr14-29626508-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 375740.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKD1	NM_002742.3	c.1774G>A	p.Gly592Arg	missense_variant	12/18	ENST00000331968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKD1	ENST00000331968.11	c.1774G>A	p.Gly592Arg	missense_variant	12/18	1	NM_002742.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital heart defects and ectodermal dysplasia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D;D;T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;.;D
M_CAP	Pathogenic	0.56	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	4.1	H;H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-7.6	.;D;D
REVEL	Pathogenic	0.97
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.97
MutPred		0.90		Gain of MoRF binding (P = 0.0817);Gain of MoRF binding (P = 0.0817);.;
MVP		0.98
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.98
gMVP		0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519635; hg19: chr14-30095714;