3-64198805-C-G

Variant names:

• chr3-64198805-C-G
• rs727504106
• NM_198859.4:c.123G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_198859.4(PRICKLE2):​c.123G>C​(p.Pro41Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P41P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PRICKLE2 NM_198859.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• 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-AS3 (HGNC:40918): (PRICKLE2 antisense RNA 3)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.

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.123G>C	p.Pro41Pro	synonymous	Exon 2 of 8	NP_942559.1	Q7Z3G6
	PRICKLE2	NM_001370528.1		c.123G>C	p.Pro41Pro	synonymous	Exon 2 of 8	NP_001357457.1	Q7Z3G6
	PRICKLE2-AS3	NR_046702.1		n.336C>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.123G>C	p.Pro41Pro	synonymous	Exon 2 of 8	ENSP00000492363.1	Q7Z3G6
	PRICKLE2	ENST00000295902.11	TSL:5	c.291G>C	p.Pro97Pro	synonymous	Exon 3 of 9	ENSP00000295902.7	A0A1X7SBR1
	PRICKLE2	ENST00000906078.1		c.123G>C	p.Pro41Pro	synonymous	Exon 2 of 9	ENSP00000576137.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461866 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-1.7

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

Other links and lift over

dbSNP: rs727504106; hg19: chr3-64184481;