3-64157183-C-T

Variant names:

• chr3-64157183-C-T
• rs17720698
• NM_198859.4:c.579G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_198859.4(PRICKLE2):​c.579G>A​(p.Pro193Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,502 control chromosomes in the GnomAD database, including 42,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4464 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37843 hom.)
• Consequence: PRICKLE2 NM_198859.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.71
• Publications: 14 publications found

Genes affected

PRICKLE2 (HGNC:20340): (prickle planar cell polarity protein 2) This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5. [provided by RefSeq, Dec 2011]

PRICKLE2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 3-64157183-C-T is Benign according to our data. Variant chr3-64157183-C-T is described in ClinVar as Benign. ClinVar VariationId is 130034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198859.4. 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
	PRICKLE2	NM_198859.4	MANE Select	c.579G>A	p.Pro193Pro	synonymous	Exon 5 of 8	NP_942559.1	Q7Z3G6
	PRICKLE2	NM_001370528.1		c.579G>A	p.Pro193Pro	synonymous	Exon 5 of 8	NP_001357457.1	Q7Z3G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.579G>A	p.Pro193Pro	synonymous	Exon 5 of 8	ENSP00000492363.1	Q7Z3G6
	PRICKLE2	ENST00000295902.11	TSL:5	c.747G>A	p.Pro249Pro	synonymous	Exon 6 of 9	ENSP00000295902.7	A0A1X7SBR1
	PRICKLE2	ENST00000906078.1		c.579G>A	p.Pro193Pro	synonymous	Exon 5 of 9	ENSP00000576137.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35551 AN: 152072 Hom.: 4457 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.200 AC: 50179 AN: 250800 AF XY: 0.203

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.00577

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.222 AC: 324054 AN: 1461312 Hom.: 37843 Cov.: 36 AF XY: 0.222 AC XY: 161256 AN XY: 726992

African (AFR) AF: 0.278 AC: 9309 AN: 33456

American (AMR) AF: 0.112 AC: 4996 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5800 AN: 26130

East Asian (EAS) AF: 0.00652 AC: 259 AN: 39698

South Asian (SAS) AF: 0.180 AC: 15525 AN: 86234

European-Finnish (FIN) AF: 0.305 AC: 16278 AN: 53400

Middle Eastern (MID) AF: 0.158 AC: 910 AN: 5754

European-Non Finnish (NFE) AF: 0.232 AC: 258258 AN: 1111562

Other (OTH) AF: 0.211 AC: 12719 AN: 60364

GnomAD4 genome AF: 0.234 AC: 35607 AN: 152190 Hom.: 4464 Cov.: 33 AF XY: 0.235 AC XY: 17502 AN XY: 74400

African (AFR) AF: 0.274 AC: 11391 AN: 41518

American (AMR) AF: 0.158 AC: 2415 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3470

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5186

South Asian (SAS) AF: 0.176 AC: 851 AN: 4822

European-Finnish (FIN) AF: 0.319 AC: 3381 AN: 10588

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16165 AN: 67988

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.229 Hom.: 17066

Bravo AF: 0.221

Asia WGS AF: 0.119 AC: 417 AN: 3478

EpiCase AF: 0.224

EpiControl AF: 0.222

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Progressive myoclonic epilepsy (1)
-	-	1	Progressive myoclonic epilepsy type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.017
DANN	Benign	0.65
PhyloP100		-3.7
Mutation Taster		=98/2	polymorphism (auto)

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: rs17720698; hg19: chr3-64142859; COSMIC: COSV55766431; COSMIC: COSV55766431;