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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G268C) has been classified as Uncertain significance.

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

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

Sel.	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	O95876-1
	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

Sel.	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	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.802G>A	p.Gly268Ser	missense	Exon 9 of 14	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000398544.7	TSL:1	c.325G>A	p.Gly109Ser	missense	Exon 3 of 12	ENSP00000381552.3	O95876-3

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 15 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

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;