3-64094189-T-TA

Variant names:

• chr3-64094189-T-TA
• rs571451772
• NM_198859.4:c.*4861dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_198859.4(PRICKLE2):​c.*4861dupT 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:):

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.*4861dupT		3_prime_UTR_variant	Exon 8 of 8	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.*4861dupT		3_prime_UTR_variant	Exon 8 of 8		NP_001357457.1
PRICKLE2-AS1	NR_045697.1	n.199-896dupA		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394	c.*4861dupT		3_prime_UTR_variant	Exon 8 of 8	1	NM_198859.4	ENSP00000492363.1
PRICKLE2-AS1	ENST00000482609.1	n.199-896dupA		intron_variant	Intron 1 of 2	1
PRICKLE2	ENST00000295902	c.*4861dupT		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000295902.7
PRICKLE2	ENST00000564377	c.*4861dupT		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000455004.2

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;