2-63259294-C-T

Variant names:

• chr2-63259294-C-T
• rs992214
• NM_015910.7:c.1915+13G>A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_015910.7(WDPCP):​c.1915+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,600,990 control chromosomes in the GnomAD database, including 249,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (33809 hom., cov: 32)
  • Exomes 𝑓: 0.53 (215679 hom.)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.434

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-63259294-C-T is Benign according to our data. Variant chr2-63259294-C-T is described in ClinVar as [Benign]. Clinvar id is 95744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-63259294-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.1915+13G>A		intron_variant	Intron 14 of 17	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12	c.1915+13G>A		intron_variant	Intron 14 of 17	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97256 AN: 151910 Hom.: 33761 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.634

GnomAD3 exomes AF: 0.604 AC: 149498 AN: 247674 Hom.: 48003 AF XY: 0.599 AC XY: 80608 AN XY: 134488

Gnomad AFR exome AF: 0.903

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.854

Gnomad SAS exome AF: 0.724

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.534 AC: 773420 AN: 1448962 Hom.: 215679 Cov.: 29 AF XY: 0.538 AC XY: 388183 AN XY: 721810

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.853

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.640 AC: 97362 AN: 152028 Hom.: 33809 Cov.: 32 AF XY: 0.639 AC XY: 47469 AN XY: 74266

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.639

Alfa AF: 0.570 Hom.: 5795

Bravo AF: 0.667

Asia WGS AF: 0.799 AC: 2775 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 1 Benign:2

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 15 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

May 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Heart defect - tongue hamartoma - polysyndactyly syndrome Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs992214; hg19: chr2-63486429;