rs10187013

Variant names:

• chr2-63831685-A-G
• rs10187013
• XM_047444626.1:c.-4903+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

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

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

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000289943 (HGNC:):

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000816213.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289943	ENST00000816213.1		n.751+8358T>C		intron	N/A
	ENSG00000289943	ENST00000816214.1		n.791+8358T>C		intron	N/A
	ENSG00000289943	ENST00000816215.1		n.378+8358T>C		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10187013;

hg19: chr2-64058819;

COSMIC: COSV71962424;