rs17720698

Positions:

• chr3-64157183-C-G
• chr3-64157183-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198859.4(PRICKLE2):​c.579G>C​(p.Pro193Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P193P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRICKLE2 NM_198859.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.579G>C	p.Pro193Pro	synonymous_variant	5/8	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.579G>C	p.Pro193Pro	synonymous_variant	5/8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.579G>C	p.Pro193Pro	synonymous_variant	5/8	1	NM_198859.4	ENSP00000492363.1
PRICKLE2	ENST00000295902.11	c.747G>C	p.Pro249Pro	synonymous_variant	6/9	5		ENSP00000295902.7
PRICKLE2	ENST00000564377.6	c.579G>C	p.Pro193Pro	synonymous_variant	5/8	5		ENSP00000455004.2
PRICKLE2	ENST00000640303.1	n.1218G>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250800 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135604

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461706 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0050
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17720698; hg19: chr3-64142859;