19-46674672-G-C

Variant names:

• chr19-46674672-G-C
• rs1322375437
• NM_016457.5:c.2488C>G

Variant summary

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

The NM_016457.5(PRKD2):​c.2488C>G​(p.His830Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,342 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H830Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRKD2 NM_016457.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.08

Genes affected

PRKD2 (HGNC:17293): (protein kinase D2) The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases. This kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

DACT3-AS1 (HGNC:44120): (DACT3 antisense RNA 1)

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 rank	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.2488C>G	p.His830Asp	missense_variant	Exon 18 of 18	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.2488C>G	p.His830Asp	missense_variant	Exon 18 of 18	1	NM_016457.5	ENSP00000291281.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454342 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	.;D;D;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	.;.;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Uncertain	-0.016	T
MutationAssessor	Pathogenic	2.9	.;M;M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.3	.;D;D;.;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0060	.;D;D;.;.
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.65
MutPred		0.34		.;Gain of disorder (P = 0.0896);Gain of disorder (P = 0.0896);.;.;
MVP		0.61
MPC		0.58
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.53
gMVP		0.89

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: rs1322375437; hg19: chr19-47177929;