19-46678631-G-C

Variant names:

• chr19-46678631-G-C
• rs926442685
• NM_016457.5:c.2103C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016457.5(PRKD2):​c.2103C>G​(p.Ile701Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,456,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PRKD2 NM_016457.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKD2	NM_016457.5	c.2103C>G	p.Ile701Met	missense_variant	Exon 16 of 18	ENST00000291281.9	NP_057541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKD2	ENST00000291281.9	c.2103C>G	p.Ile701Met	missense_variant	Exon 16 of 18	1	NM_016457.5	ENSP00000291281.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1456538 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 724922

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: 0.0000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2103C>G (p.I701M) alteration is located in exon 16 (coding exon 16) of the PRKD2 gene. This alteration results from a C to G substitution at nucleotide position 2103, causing the isoleucine (I) at amino acid position 701 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T;T;.;.
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	.;L;L;.;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.8	.;D;D;.;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	.;D;D;.;.
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.84
MutPred		0.39		.;Gain of disorder (P = 0.1067);Gain of disorder (P = 0.1067);.;Gain of disorder (P = 0.1067);
MVP		0.72
MPC		2.6
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.099
gMVP		0.78

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: rs926442685; hg19: chr19-47181888;