14-29577259-A-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002742.3(PRKD1):c.2718T>G(p.Gly906=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,613,390 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (3 hom.)
• Consequence: PRKD1 NM_002742.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.443

Genes affected

PRKD1 (HGNC:9407): (protein kinase D1) The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-29577259-A-C is Benign according to our data. Variant chr14-29577259-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 720359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.443 with no splicing effect.
• BS2: High AC in GnomAd at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKD1	NM_002742.3	c.2718T>G	p.Gly906=	synonymous_variant	18/18	ENST00000331968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKD1	ENST00000331968.11	c.2718T>G	p.Gly906=	synonymous_variant	18/18	1	NM_002742.3	P3

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000718 AC: 180 AN: 250810 Hom.: 1 AF XY: 0.000996 AC XY: 135 AN XY: 135530

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00408

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000336

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000411 AC: 601 AN: 1461110 Hom.: 3 Cov.: 31 AF XY: 0.000542 AC XY: 394 AN XY: 726888

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00393

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74448

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000136

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	PRKD1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.4
Dann	Benign	0.69

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: rs139896732; hg19: chr14-30046465;