chr3-64093959-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_198859.4(PRICKLE2):​c.*5092T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 152,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Consequence

PRICKLE2
NM_198859.4 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRICKLE2NM_198859.4 linkuse as main transcriptc.*5092T>C 3_prime_UTR_variant 8/8 ENST00000638394.2
PRICKLE2-AS1NR_045697.1 linkuse as main transcriptn.199-1135A>G intron_variant, non_coding_transcript_variant
PRICKLE2NM_001370528.1 linkuse as main transcriptc.*5092T>C 3_prime_UTR_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRICKLE2ENST00000638394.2 linkuse as main transcriptc.*5092T>C 3_prime_UTR_variant 8/81 NM_198859.4
PRICKLE2-AS1ENST00000482609.1 linkuse as main transcriptn.199-1135A>G intron_variant, non_coding_transcript_variant 1
PRICKLE2ENST00000295902.11 linkuse as main transcriptc.*5092T>C 3_prime_UTR_variant 9/95 P1
PRICKLE2ENST00000564377.6 linkuse as main transcriptc.*5092T>C 3_prime_UTR_variant 8/85

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152050
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152050
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.000170
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.17
CADD
Benign
16
DANN
Benign
0.91

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1056419773; hg19: chr3-64079635; API