ENST00000467687.1:n.309-45589C>T

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	XM_047444626.1	c.-4816-18174C>T		intron_variant	Intron 2 of 20		XP_047300582.1
WDPCP	XM_047444627.1	c.-429-45589C>T		intron_variant	Intron 2 of 19		XP_047300583.1
WDPCP	XM_047444628.1	c.-250+117195C>T		intron_variant	Intron 2 of 18		XP_047300584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000467687.1	n.309-45589C>T		intron_variant	Intron 2 of 4	5
WDPCP	ENST00000490935.5	n.403+15070C>T		intron_variant	Intron 3 of 7	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

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 v4.3

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;