2-37274422-G-C

Position:

• chr2-37274422-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005813.6(PRKD3):​c.1650C>G​(p.His550Gln) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRKD3 NM_005813.6 missense, splice_region
• Scores: Splicing: ADA: 0.9832
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46

Genes affected

PRKD3 (HGNC:9408): (protein kinase D3) This gene belongs to the multigene protein kinase D family of serine/threonine kinases, which bind diacylglycerol and phorbol esters. Members of this family are characterized by an N-terminal regulatory domain comprised of a tandem repeat of cysteine-rich zinc-finger motifs and a pleckstrin domain. The C-terminal region contains the catalytic domain and is distantly related to calcium-regulated kinases. Catalytic activity of this enzyme promotes its nuclear localization. This protein has been implicated in a variety of functions including negative regulation of human airway epithelial barrier formation, growth regulation of breast and prostate cancer cells, and vesicle trafficking. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKD3	NM_005813.6	c.1650C>G	p.His550Gln	missense_variant, splice_region_variant	11/19	ENST00000234179.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKD3	ENST00000234179.8	c.1650C>G	p.His550Gln	missense_variant, splice_region_variant	11/19	1	NM_005813.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.13
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.57	T;T;.
Polyphen		0.017	B;B;.
Vest4		0.62
MutPred		0.20		Gain of methylation at K548 (P = 0.0883);Gain of methylation at K548 (P = 0.0883);.;
MVP		0.82
MPC		0.27
ClinPred		0.87	D
GERP RS		4.7
Varity_R		0.37
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.76
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-37501565;