rs262474

Positions:

• chr2-63607485-A-G

Variant summary

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

The XM_047444626.1(WDPCP):​c.-249-35859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 151,654 control chromosomes in the GnomAD database, including 49,766 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 0.80 (49766 hom., cov: 28)
• Consequence: WDPCP XM_047444626.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	XM_047444626.1	c.-249-35859T>C		intron_variant			XP_047300582.1
WDPCP	XM_047444627.1	c.-249-35859T>C		intron_variant			XP_047300583.1
WDPCP	XM_047444628.1	c.-249-35859T>C		intron_variant			XP_047300584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000467687.1	n.488+43174T>C		intron_variant, non_coding_transcript_variant		5
WDPCP	ENST00000490935.5	n.583+43174T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121894 AN: 151534 Hom.: 49694 Cov.: 28

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.805 AC: 122031 AN: 151654 Hom.: 49766 Cov.: 28 AF XY: 0.808 AC XY: 59876 AN XY: 74082

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.772

Alfa AF: 0.749 Hom.: 5360

Bravo AF: 0.812

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs262474; hg19: chr2-63834619;