chr19-46704397-G-A

Variant names:

• chr19-46704397-G-A
• rs11083846
• NM_016457.5:c.667-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016457.5(PRKD2):​c.667-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,770 control chromosomes in the GnomAD database, including 36,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2420 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34205 hom.)
• Consequence: PRKD2 NM_016457.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003207
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.608
• Publications: 67 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-46704397-G-A is Benign according to our data. Variant chr19-46704397-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	NM_016457.5	MANE Select	c.667-6C>T		splice_region intron	N/A	NP_057541.2
	PRKD2	NM_001079880.2		c.667-6C>T		splice_region intron	N/A	NP_001073349.1
	PRKD2	NM_001079881.2		c.667-6C>T		splice_region intron	N/A	NP_001073350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD2	ENST00000291281.9	TSL:1 MANE Select	c.667-6C>T		splice_region intron	N/A	ENSP00000291281.3
	PRKD2	ENST00000595515.5	TSL:2	c.667-6C>T		splice_region intron	N/A	ENSP00000470804.1
	PRKD2	ENST00000433867.5	TSL:5	c.667-6C>T		splice_region intron	N/A	ENSP00000393978.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24468 AN: 152080 Hom.: 2420 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.173 AC: 43299 AN: 250810 AF XY: 0.179

Gnomad AFR exome AF: 0.0637

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.209 AC: 305914 AN: 1461572 Hom.: 34205 Cov.: 36 AF XY: 0.209 AC XY: 152133 AN XY: 727064

African (AFR) AF: 0.0615 AC: 2059 AN: 33480

American (AMR) AF: 0.106 AC: 4752 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5704 AN: 26136

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39700

South Asian (SAS) AF: 0.183 AC: 15747 AN: 86258

European-Finnish (FIN) AF: 0.184 AC: 9765 AN: 53150

Middle Eastern (MID) AF: 0.230 AC: 1328 AN: 5768

European-Non Finnish (NFE) AF: 0.229 AC: 254972 AN: 1111966

Other (OTH) AF: 0.191 AC: 11563 AN: 60392

GnomAD4 genome AF: 0.161 AC: 24470 AN: 152198 Hom.: 2420 Cov.: 32 AF XY: 0.159 AC XY: 11829 AN XY: 74420

African (AFR) AF: 0.0656 AC: 2726 AN: 41536

American (AMR) AF: 0.143 AC: 2181 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5176

South Asian (SAS) AF: 0.167 AC: 805 AN: 4830

European-Finnish (FIN) AF: 0.179 AC: 1903 AN: 10608

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15356 AN: 67974

Other (OTH) AF: 0.199 AC: 420 AN: 2114

Alfa AF: 0.210 Hom.: 12964

Bravo AF: 0.153

Asia WGS AF: 0.0620 AC: 217 AN: 3478

EpiCase AF: 0.235

EpiControl AF: 0.220

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.77
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs11083846; hg19: chr19-47207654; COSMIC: COSV52188503; COSMIC: COSV52188503;