rs2837269

Positions:

• chr21-39888016-A-G
• chr21-39888016-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006198.3(PCP4):​c.10-10460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,024 control chromosomes in the GnomAD database, including 12,547 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12547 hom., cov: 32)
• Consequence: PCP4 NM_006198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945

Genes affected

PCP4 (HGNC:8742): (Purkinje cell protein 4) Enables calcium ion binding activity and calmodulin binding activity. Involved in calmodulin dependent kinase signaling pathway and positive regulation of neuron differentiation. Located in cytosol and nucleus. Part of protein-containing complex. Biomarker of Huntington's disease and leiomyoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCP4	NM_006198.3	c.10-10460A>G		intron_variant		ENST00000328619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCP4	ENST00000328619.10	c.10-10460A>G		intron_variant		1	NM_006198.3	P1
PCP4	ENST00000462224.5	c.10-10460A>G		intron_variant, NMD_transcript_variant		2
PCP4	ENST00000468717.5	n.240+4384A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60041 AN: 151906 Hom.: 12532 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.395 AC: 60095 AN: 152024 Hom.: 12547 Cov.: 32 AF XY: 0.402 AC XY: 29879 AN XY: 74312

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.391

Alfa AF: 0.350 Hom.: 12291

Bravo AF: 0.393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.56

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: rs2837269; hg19: chr21-41259941;