2-63610517-A-G

Variant names:

• chr2-63610517-A-G
• rs262490
• ENST00000467687.1:n.488+40142T>C

Variant summary

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

The ENST00000467687.1(WDPCP):​n.488+40142T>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 151,856 control chromosomes in the GnomAD database, including 49,847 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 (49847 hom., cov: 29)
• Consequence: WDPCP ENST00000467687.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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=-0.92).
• 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 rank	MANE	Protein	UniProt
WDPCP	XM_047444626.1	c.-249-38891T>C		intron_variant	Intron 4 of 20		XP_047300582.1
WDPCP	XM_047444627.1	c.-249-38891T>C		intron_variant	Intron 3 of 19		XP_047300583.1
WDPCP	XM_047444628.1	c.-249-38891T>C		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.488+40142T>C		intron_variant	Intron 3 of 4	5
WDPCP	ENST00000490935.5	n.583+40142T>C		intron_variant	Intron 4 of 7	5

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122077 AN: 151738 Hom.: 49777 Cov.: 29

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.839

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: 0.759

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.805 AC: 122211 AN: 151856 Hom.: 49847 Cov.: 29 AF XY: 0.808 AC XY: 59984 AN XY: 74216

African (AFR) AF: 0.924 AC: 38288 AN: 41422

American (AMR) AF: 0.826 AC: 12613 AN: 15268

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

East Asian (EAS) AF: 0.982 AC: 5084 AN: 5178

South Asian (SAS) AF: 0.835 AC: 3994 AN: 4786

European-Finnish (FIN) AF: 0.779 AC: 8177 AN: 10500

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

European-Non Finnish (NFE) AF: 0.717 AC: 48676 AN: 67912

Other (OTH) AF: 0.772 AC: 1632 AN: 2114

Alfa AF: 0.751 Hom.: 5308

Bravo AF: 0.812

Asia WGS AF: 0.903 AC: 3128 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.062

Splicing

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

Other links and lift over

dbSNP: rs262490; hg19: chr2-63837651;