rs10187013

Variant names:

• chr2-63831685-A-G
• rs10187013
• ENST00000816213.1:n.751+8358T>C

Variant summary

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

The ENST00000816213.1(ENSG00000289943):​n.751+8358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 148,922 control chromosomes in the GnomAD database, including 5,003 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 0.22 (5003 hom., cov: 32)
• Consequence: ENSG00000289943 ENST00000816213.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 publications found

Genes affected

ENSG00000289943 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	XM_047444626.1	c.-4903+8358T>C		intron_variant	Intron 1 of 20		XP_047300582.1
WDPCP	XM_047444627.1	c.-516+8358T>C		intron_variant	Intron 1 of 19		XP_047300583.1
WDPCP	XM_047444629.1	c.-430+8358T>C		intron_variant	Intron 1 of 18		XP_047300585.1
WDPCP	XM_047444631.1	c.-430+8358T>C		intron_variant	Intron 1 of 19		XP_047300587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289943	ENST00000816213.1	n.751+8358T>C		intron_variant	Intron 1 of 2
ENSG00000289943	ENST00000816214.1	n.791+8358T>C		intron_variant	Intron 1 of 1
ENSG00000289943	ENST00000816215.1	n.378+8358T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33418 AN: 148858 Hom.: 5003 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.225 AC: 33441 AN: 148922 Hom.: 5003 Cov.: 32 AF XY: 0.231 AC XY: 16737 AN XY: 72606

African (AFR) AF: 0.110 AC: 4436 AN: 40362

American (AMR) AF: 0.303 AC: 4547 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 718 AN: 3430

East Asian (EAS) AF: 0.781 AC: 4026 AN: 5158

South Asian (SAS) AF: 0.384 AC: 1837 AN: 4778

European-Finnish (FIN) AF: 0.245 AC: 2418 AN: 9882

Middle Eastern (MID) AF: 0.243 AC: 68 AN: 280

European-Non Finnish (NFE) AF: 0.217 AC: 14546 AN: 67048

Other (OTH) AF: 0.235 AC: 487 AN: 2072

Alfa AF: 0.217 Hom.: 2894

Bravo AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs10187013; hg19: chr2-64058819; COSMIC: COSV71962424;