3-64094189-T-TA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_198859.4(PRICKLE2):c.*4861_*4862insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 151,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRICKLE2 NM_198859.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

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-AS1 (HGNC:40916): (PRICKLE2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000271 (41/151476) while in subpopulation EAS AF= 0.000581 (3/5160). AF 95% confidence interval is 0.000231. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.*4861_*4862insT		3_prime_UTR_variant	8/8	ENST00000638394.2
PRICKLE2-AS1	NR_045697.1	n.199-896dup		intron_variant, non_coding_transcript_variant
PRICKLE2	NM_001370528.1	c.*4861_*4862insT		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.*4861_*4862insT		3_prime_UTR_variant	8/8	1	NM_198859.4
PRICKLE2-AS1	ENST00000482609.1	n.199-896dup		intron_variant, non_coding_transcript_variant		1
PRICKLE2	ENST00000295902.11	c.*4861_*4862insT		3_prime_UTR_variant	9/9	5		P1
PRICKLE2	ENST00000564377.6	c.*4861_*4862insT		3_prime_UTR_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 42 AN: 151362 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.0000958

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.000482

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000271 AC: 41 AN: 151476 Hom.: 0 Cov.: 33 AF XY: 0.000284 AC XY: 21 AN XY: 74014

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.0000958

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000283

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive myoclonic epilepsy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs571451772; hg19: chr3-64079865;