rs1555825242

Variant names:

• chr19-46675103-T-C
• rs1555825242
• NM_016457.5:c.2354A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_016457.5(PRKD2):​c.2354A>G​(p.Asn785Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PRKD2 NM_016457.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34741056).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	NM_016457.5	MANE Select	c.2354A>G	p.Asn785Ser	missense	Exon 17 of 18	NP_057541.2
	PRKD2	NM_001079880.2		c.2354A>G	p.Asn785Ser	missense	Exon 18 of 19	NP_001073349.1	Q9BZL6-1
	PRKD2	NM_001079881.2		c.2354A>G	p.Asn785Ser	missense	Exon 18 of 19	NP_001073350.1	Q9BZL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	ENST00000291281.9	TSL:1 MANE Select	c.2354A>G	p.Asn785Ser	missense	Exon 17 of 18	ENSP00000291281.3	Q9BZL6-1
	PRKD2	ENST00000597390.5	TSL:1	n.*414A>G		non_coding_transcript_exon	Exon 8 of 9	ENSP00000472913.1	M0R2Z8
	PRKD2	ENST00000597390.5	TSL:1	n.*414A>G		3_prime_UTR	Exon 8 of 9	ENSP00000472913.1	M0R2Z8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000816 AC: 2 AN: 245188 AF XY: 0.00000756

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458484 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725122

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000585 AC: 5 AN: 85426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110256

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	0.053
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.30	N
PhyloP100		8.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.24
Sift	Benign	0.079	T
Sift4G	Benign	0.16	T
Polyphen		0.77	P
Vest4		0.48
MutPred		0.48		Gain of MoRF binding (P = 0.1096)
MVP		0.50
MPC		2.3
ClinPred		0.71	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.33
gMVP		0.91
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1555825242; hg19: chr19-47178360;