rs1555825242

Variant names:

• chr19-46675103-T-A
• NM_016457.5:c.2354A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-46675103-T-A
• chr19-46675103-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016457.5(PRKD2):​c.2354A>T​(p.Asn785Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 7.96

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.2354A>T	p.Asn785Ile	missense_variant	Exon 17 of 18	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.2354A>T	p.Asn785Ile	missense_variant	Exon 17 of 18	1	NM_016457.5	ENSP00000291281.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458484 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725122

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	.;.;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.3	.;L;L;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.5	.;D;D;.;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	.;D;D;.;.
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		0.99	.;D;D;.;.
Vest4		0.78
MutPred		0.63		.;Loss of MoRF binding (P = 0.1374);Loss of MoRF binding (P = 0.1374);.;.;
MVP		0.72
MPC		2.8
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.69
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr19-47178360;