3-64180014-C-G

Variant names:

• chr3-64180014-C-G
• rs695936
• NM_198859.4:c.145-16885G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198859.4(PRICKLE2):​c.145-16885G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,170 control chromosomes in the GnomAD database, including 3,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3084 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.145-16885G>C		intron_variant	Intron 2 of 7	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.145-16885G>C		intron_variant	Intron 2 of 7		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.145-16885G>C		intron_variant	Intron 2 of 7	1	NM_198859.4	ENSP00000492363.1
PRICKLE2	ENST00000295902.11	c.313-16885G>C		intron_variant	Intron 3 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000564377.6	c.145-16885G>C		intron_variant	Intron 2 of 7	5		ENSP00000455004.2
PRICKLE2	ENST00000498162.2	c.292-16885G>C		intron_variant	Intron 3 of 4	5		ENSP00000419951.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28292 AN: 152052 Hom.: 3071 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28320 AN: 152170 Hom.: 3084 Cov.: 33 AF XY: 0.185 AC XY: 13764 AN XY: 74418

African (AFR) AF: 0.247 AC: 10246 AN: 41510

American (AMR) AF: 0.181 AC: 2771 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2513 AN: 5160

South Asian (SAS) AF: 0.201 AC: 971 AN: 4830

European-Finnish (FIN) AF: 0.0897 AC: 950 AN: 10596

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9654 AN: 68010

Other (OTH) AF: 0.182 AC: 385 AN: 2110

Alfa AF: 0.163 Hom.: 256

Bravo AF: 0.198

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		-0.16
Mutation Taster		=100/0	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: rs695936; hg19: chr3-64165690;