14-29578374-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002742.3(PRKD1):c.2435-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,583,670 control chromosomes in the GnomAD database, including 426,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38593 hom., cov: 28)
  • Exomes 𝑓: 0.73 (388297 hom.)
• Consequence: PRKD1 NM_002742.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-29578374-C-T is Benign according to our data. Variant chr14-29578374-C-T is described in ClinVar as [Benign]. Clinvar id is 1327445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKD1	NM_002742.3	c.2435-14G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000331968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKD1	ENST00000331968.11	c.2435-14G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002742.3	P3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 107725 AN: 151264 Hom.: 38558 Cov.: 28

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.694

GnomAD3 exomes AF: 0.682 AC: 165152 AN: 242046 Hom.: 57073 AF XY: 0.680 AC XY: 89174 AN XY: 131096

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.567

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.680

GnomAD4 exome AF: 0.733 AC: 1049820 AN: 1432288 Hom.: 388297 Cov.: 26 AF XY: 0.728 AC XY: 519537 AN XY: 713356

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.668

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.709

GnomAD4 genome AF: 0.712 AC: 107816 AN: 151382 Hom.: 38593 Cov.: 28 AF XY: 0.704 AC XY: 52036 AN XY: 73964

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.696

Alfa AF: 0.719 Hom.: 7883

Bravo AF: 0.714

Asia WGS AF: 0.570 AC: 1979 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital heart defects and ectodermal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	11
Dann	Benign	0.52

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: rs2273815; hg19: chr14-30047580; COSMIC: COSV59559784;