2-63696427-G-A

Variant names:

• chr2-63696427-G-A
• rs6546025
• ENST00000467687.1:n.309-45589C>T

Variant summary

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

The ENST00000467687.1(WDPCP):​n.309-45589C>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 ENST00000467687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 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.309-45589C>T		intron	N/A
	WDPCP	ENST00000490935.5	TSL:5	n.403+15070C>T		intron	N/A

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

African (AFR) AF: 0.860 AC: 35689 AN: 41504

American (AMR) AF: 0.683 AC: 10421 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1246 AN: 5162

South Asian (SAS) AF: 0.637 AC: 3065 AN: 4808

European-Finnish (FIN) AF: 0.780 AC: 8248 AN: 10580

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.783 AC: 53230 AN: 67964

Other (OTH) AF: 0.761 AC: 1608 AN: 2112

Alfa AF: 0.776 Hom.: 56191

Bravo AF: 0.762

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs6546025; hg19: chr2-63923561;