3-64157303-AAC-TAT

Variant names:

• chr3-64157303-AAC-TAT
• NM_198859.4:c.457_459delGTTinsATA
• PRICKLE2 p.Val153Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_198859.4(PRICKLE2):​c.457_459delGTTinsATA​(p.Val153Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRICKLE2 NM_198859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.13
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	NM_198859.4	MANE Select	c.457_459delGTTinsATA	p.Val153Ile	missense	N/A	NP_942559.1	Q7Z3G6
	PRICKLE2	NM_001370528.1		c.457_459delGTTinsATA	p.Val153Ile	missense	N/A	NP_001357457.1	Q7Z3G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.457_459delGTTinsATA	p.Val153Ile	missense	N/A	ENSP00000492363.1	Q7Z3G6
	PRICKLE2	ENST00000295902.11	TSL:5	c.625_627delGTTinsATA	p.Val209Ile	missense	N/A	ENSP00000295902.7	A0A1X7SBR1
	PRICKLE2	ENST00000906078.1		c.457_459delGTTinsATA	p.Val153Ile	missense	N/A	ENSP00000576137.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-64142979;