rs17617459

Variant names:

• chr2-63433768-C-T
• rs17617459
• NM_015910.7:c.802G>A

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.802G>A​(p.Gly268Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,612,906 control chromosomes in the GnomAD database, including 3,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (233 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2797 hom.)
• Consequence: WDPCP NM_015910.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.648
• Publications: 13 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019892156).
• BP6: Variant 2-63433768-C-T is Benign according to our data. Variant chr2-63433768-C-T is described in ClinVar as Benign. ClinVar VariationId is 260683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015910.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	NM_015910.7	MANE Select	c.802G>A	p.Gly268Ser	missense	Exon 9 of 18	NP_056994.3
	WDPCP	NM_001354044.2		c.730G>A	p.Gly244Ser	missense	Exon 10 of 19	NP_001340973.1
	WDPCP	NM_001354045.2		c.802G>A	p.Gly268Ser	missense	Exon 9 of 13	NP_001340974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.802G>A	p.Gly268Ser	missense	Exon 9 of 18	ENSP00000272321.7
	WDPCP	ENST00000409562.7	TSL:1	c.802G>A	p.Gly268Ser	missense	Exon 9 of 14	ENSP00000387222.3
	WDPCP	ENST00000398544.7	TSL:1	c.325G>A	p.Gly109Ser	missense	Exon 3 of 12	ENSP00000381552.3

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6565 AN: 151910 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0302

GnomAD2 exomes AF: 0.0461 AC: 11470 AN: 248750 AF XY: 0.0462

Gnomad AFR exome AF: 0.00943

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.000279

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0422

GnomAD4 exome AF: 0.0565 AC: 82473 AN: 1460878 Hom.: 2797 Cov.: 31 AF XY: 0.0555 AC XY: 40351 AN XY: 726682

African (AFR) AF: 0.00914 AC: 306 AN: 33462

American (AMR) AF: 0.0151 AC: 674 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 528 AN: 26110

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39686

South Asian (SAS) AF: 0.0210 AC: 1809 AN: 86028

European-Finnish (FIN) AF: 0.112 AC: 5971 AN: 53374

Middle Eastern (MID) AF: 0.0161 AC: 93 AN: 5768

European-Non Finnish (NFE) AF: 0.0633 AC: 70389 AN: 1111416

Other (OTH) AF: 0.0447 AC: 2697 AN: 60362

GnomAD4 genome AF: 0.0432 AC: 6564 AN: 152028 Hom.: 233 Cov.: 32 AF XY: 0.0439 AC XY: 3261 AN XY: 74316

African (AFR) AF: 0.0105 AC: 437 AN: 41466

American (AMR) AF: 0.0235 AC: 359 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4810

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10554

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4294 AN: 67970

Other (OTH) AF: 0.0294 AC: 62 AN: 2108

Alfa AF: 0.0501 Hom.: 729

Bravo AF: 0.0352

TwinsUK AF: 0.0806 AC: 299

ALSPAC AF: 0.0688 AC: 265

ESP6500AA AF: 0.0111 AC: 41

ESP6500EA AF: 0.0598 AC: 490

ExAC AF: 0.0474 AC: 5723

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Bardet-Biedl syndrome 15 Benign:1

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.

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.65
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.037
Sift	Benign	0.49	T
Sift4G	Benign	0.64	T
Polyphen		0.010	B
Vest4		0.065
MPC		0.15
ClinPred		0.0023	T
GERP RS		4.6
Varity_R		0.061
gMVP		0.33
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17617459; hg19: chr2-63660902;