rs139355024

Variant names:

• chr14-29597503-T-C
• rs139355024
• NM_002742.3:c.2422A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-29597503-T-C
• chr14-29597503-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002742.3(PRKD1):​c.2422A>G​(p.Ile808Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,602,962 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: PRKD1 NM_002742.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.68
• Publications: 1 publications found

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]

PRKD1 Gene-Disease associations (from GenCC):

• congenital heart defects and ectodermal dysplasia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart defects, multiple types

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

LOC124903297 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0073159635).
• BP6: Variant 14-29597503-T-C is Benign according to our data. Variant chr14-29597503-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00173 (264/152318) while in subpopulation AFR AF = 0.00621 (258/41572). AF 95% confidence interval is 0.00558. There are 2 homozygotes in GnomAd4. There are 124 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002742.3. 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
	PRKD1	NM_002742.3	MANE Select	c.2422A>G	p.Ile808Val	missense	Exon 16 of 18	NP_002733.2	Q15139
	PRKD1	NM_001330069.2		c.2446A>G	p.Ile816Val	missense	Exon 17 of 19	NP_001316998.1	F8WBA3
	PRKD1	NM_001348390.1		c.2158A>G	p.Ile720Val	missense	Exon 17 of 19	NP_001335319.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKD1	ENST00000331968.11	TSL:1 MANE Select	c.2422A>G	p.Ile808Val	missense	Exon 16 of 18	ENSP00000333568.6	Q15139
	PRKD1	ENST00000415220.6	TSL:5	c.2446A>G	p.Ile816Val	missense	Exon 17 of 19	ENSP00000390535.2	F8WBA3
	PRKD1	ENST00000490795.1	TSL:2	n.166A>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000447723.1	H0YHS9

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152200 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000443 AC: 111 AN: 250302 AF XY: 0.000274

Gnomad AFR exome AF: 0.00652

Gnomad AMR exome AF: 0.0000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000152 AC: 221 AN: 1450644 Hom.: 1 Cov.: 30 AF XY: 0.000131 AC XY: 94 AN XY: 719482

African (AFR) AF: 0.00594 AC: 198 AN: 33336

American (AMR) AF: 0.0000899 AC: 4 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39394

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102752

Other (OTH) AF: 0.000284 AC: 17 AN: 59886

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152318 Hom.: 2 Cov.: 33 AF XY: 0.00166 AC XY: 124 AN XY: 74482

African (AFR) AF: 0.00621 AC: 258 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000629 Hom.: 0

Bravo AF: 0.00197

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000610 AC: 74

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	PRKD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.17	N
PhyloP100		2.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Benign	0.25	T
Polyphen		0.10	B
Vest4		0.14
MVP		0.79
MPC		0.35
ClinPred		0.016	T
GERP RS		4.2
Varity_R		0.18
gMVP		0.46
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs139355024; hg19: chr14-30066709;