rs2421862

Variant names:

• chr2-63174838-G-A
• rs2421862
• NM_015910.7:c.1916-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015910.7(WDPCP):​c.1916-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,916 control chromosomes in the GnomAD database, including 31,676 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1984 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29692 hom.)
• Consequence: WDPCP NM_015910.7 splice_region, intron
• Scores: Splicing: ADA: 0.00003207
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.174
• Publications: 12 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

ENSG00000286480 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-63174838-G-A is Benign according to our data. Variant chr2-63174838-G-A is described in ClinVar as Benign. ClinVar VariationId is 260680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.1916-6C>T		splice_region_variant, 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.1916-6C>T		splice_region_variant, intron_variant	Intron 14 of 17	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22265 AN: 151846 Hom.: 1981 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.159 AC: 39494 AN: 249152 AF XY: 0.164

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0378

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.195 AC: 285108 AN: 1459952 Hom.: 29692 Cov.: 32 AF XY: 0.195 AC XY: 141547 AN XY: 726410

African (AFR) AF: 0.0517 AC: 1730 AN: 33450

American (AMR) AF: 0.109 AC: 4853 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4549 AN: 26124

East Asian (EAS) AF: 0.0388 AC: 1540 AN: 39662

South Asian (SAS) AF: 0.140 AC: 12076 AN: 86214

European-Finnish (FIN) AF: 0.155 AC: 8249 AN: 53380

Middle Eastern (MID) AF: 0.236 AC: 1346 AN: 5712

European-Non Finnish (NFE) AF: 0.215 AC: 239275 AN: 1110402

Other (OTH) AF: 0.191 AC: 11490 AN: 60308

GnomAD4 genome AF: 0.147 AC: 22275 AN: 151964 Hom.: 1984 Cov.: 32 AF XY: 0.145 AC XY: 10778 AN XY: 74256

African (AFR) AF: 0.0571 AC: 2372 AN: 41508

American (AMR) AF: 0.139 AC: 2129 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3466

East Asian (EAS) AF: 0.0410 AC: 212 AN: 5172

South Asian (SAS) AF: 0.139 AC: 670 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1709 AN: 10502

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13992 AN: 67926

Other (OTH) AF: 0.181 AC: 380 AN: 2102

Alfa AF: 0.188 Hom.: 2854

Bravo AF: 0.142

Asia WGS AF: 0.0990 AC: 342 AN: 3478

EpiCase AF: 0.217

EpiControl AF: 0.213

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

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

Significance: Benign

Review Status: no assertion criteria provided

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

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 15 Benign:1

Jan 13, 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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.91
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs2421862; hg19: chr2-63401973; COSMIC: COSV55419132;