chr2-63174838-G-A

Position:

• chr2-63174838-G-A

Variant summary

Our verdict is Benign. Variant got -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, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003207
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.174

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 260680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-63174838-G-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
WDPCP	NM_015910.7	c.1916-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000272321.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDPCP	ENST00000272321.12	c.1916-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015910.7	P1
	ENST00000657946.1	n.255+14596G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.159 AC: 39494 AN: 249152 Hom.: 3664 AF XY: 0.164 AC XY: 22180 AN XY: 135170

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 SAS exome AF: 0.139

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

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.0388

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.191

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

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.181

Alfa AF: 0.187 Hom.: 1911

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Bardet-Biedl syndrome 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

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