chr19-46675096-C-T

Variant names:

• chr19-46675096-C-T
• rs752652778
• NM_016457.5:c.2361G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_016457.5(PRKD2):​c.2361G>A​(p.Leu787Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,978 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PRKD2 NM_016457.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 19-46675096-C-T is Benign according to our data. Variant chr19-46675096-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 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.2361G>A	p.Leu787Leu	synonymous	Exon 17 of 18	NP_057541.2
	PRKD2	NM_001079880.2		c.2361G>A	p.Leu787Leu	synonymous	Exon 18 of 19	NP_001073349.1	Q9BZL6-1
	PRKD2	NM_001079881.2		c.2361G>A	p.Leu787Leu	synonymous	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.2361G>A	p.Leu787Leu	synonymous	Exon 17 of 18	ENSP00000291281.3	Q9BZL6-1
	PRKD2	ENST00000597390.5	TSL:1	n.*421G>A		non_coding_transcript_exon	Exon 8 of 9	ENSP00000472913.1	M0R2Z8
	PRKD2	ENST00000597390.5	TSL:1	n.*421G>A		3_prime_UTR	Exon 8 of 9	ENSP00000472913.1	M0R2Z8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000813 AC: 2 AN: 245968 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1458978 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725438

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

American (AMR) AF: 0.0000225 AC: 1 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110548

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs752652778; hg19: chr19-47178353;