rs6445398

Variant names:

• chr3-64350234-T-C
• rs6445398
• ENST00000295902.11:c.128+94249A>G

Variant summary

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

The ENST00000295902.11(PRICKLE2):​c.128+94249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,012 control chromosomes in the GnomAD database, including 3,520 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 0.18 (3520 hom., cov: 31)
• Consequence: PRICKLE2 ENST00000295902.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000295902.11	c.128+94249A>G		intron_variant	Intron 2 of 8	5		ENSP00000295902.7
PRICKLE2	ENST00000498162.2	c.107+94249A>G		intron_variant	Intron 2 of 4	5		ENSP00000419951.2
PRICKLE2	ENST00000485770.2	n.340+94249A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26569 AN: 151894 Hom.: 3503 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.175 AC: 26615 AN: 152012 Hom.: 3520 Cov.: 31 AF XY: 0.178 AC XY: 13234 AN XY: 74296

African (AFR) AF: 0.346 AC: 14318 AN: 41428

American (AMR) AF: 0.191 AC: 2921 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1952 AN: 5130

South Asian (SAS) AF: 0.146 AC: 701 AN: 4814

European-Finnish (FIN) AF: 0.110 AC: 1160 AN: 10582

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0730 AC: 4962 AN: 67992

Other (OTH) AF: 0.147 AC: 311 AN: 2110

Alfa AF: 0.0960 Hom.: 2250

Bravo AF: 0.192

Asia WGS AF: 0.281 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6445398; hg19: chr3-64335910;