rs6546025

Positions:

• chr2-63696427-G-A

Variant summary

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

The XM_047444626.1(WDPCP):​c.-4816-18174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,074 control chromosomes in the GnomAD database, including 46,265 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 0.77 (46265 hom., cov: 31)
• Consequence: WDPCP XM_047444626.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

Genes affected

WDPCP (HGNC:28027): (WD repeat containing planar cell polarity effector) This gene encodes a cytoplasmic WD40 repeat protein. A similar gene in frogs encodes a planar cell polarity protein that plays a critical role in collective cell movement and ciliogenesis by mediating septin localization. Mutations in this gene are associated with Bardet-Biedl syndrome 15 and may also play a role in Meckel-Gruber syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDPCP	XM_047444626.1	c.-4816-18174C>T		intron_variant
WDPCP	XM_047444627.1	c.-429-45589C>T		intron_variant
WDPCP	XM_047444628.1	c.-250+117195C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDPCP	ENST00000467687.1	n.309-45589C>T		intron_variant, non_coding_transcript_variant		5
WDPCP	ENST00000490935.5	n.403+15070C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117004 AN: 151958 Hom.: 46240 Cov.: 31

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.770 AC: 117074 AN: 152074 Hom.: 46265 Cov.: 31 AF XY: 0.765 AC XY: 56861 AN XY: 74338

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.761

Alfa AF: 0.776 Hom.: 42033

Bravo AF: 0.762

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6546025; hg19: chr2-63923561;