2-63609133-G-A

Variant names:

• chr2-63609133-G-A
• rs262489
• ENST00000467687.1:n.488+41526C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000467687.1(WDPCP):​n.488+41526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,070 control chromosomes in the GnomAD database, including 49,664 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 (49664 hom., cov: 31)
• Consequence: WDPCP ENST00000467687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 2 publications found

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]

WDPCP Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• heart defect - tongue hamartoma - polysyndactyly syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000467687.1	TSL:5	n.488+41526C>T		intron	N/A
	WDPCP	ENST00000490935.5	TSL:5	n.583+41526C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121945 AN: 151952 Hom.: 49594 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.803 AC: 122079 AN: 152070 Hom.: 49664 Cov.: 31 AF XY: 0.806 AC XY: 59933 AN XY: 74328

African (AFR) AF: 0.922 AC: 38266 AN: 41514

American (AMR) AF: 0.824 AC: 12582 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2757 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5067 AN: 5162

South Asian (SAS) AF: 0.832 AC: 4011 AN: 4822

European-Finnish (FIN) AF: 0.780 AC: 8235 AN: 10560

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48545 AN: 67948

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.752 Hom.: 5628

Bravo AF: 0.810

Asia WGS AF: 0.902 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.65
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs262489; hg19: chr2-63836267;