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: 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

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.

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.1916-6C>T		splice_region intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.1844-6C>T		splice_region intron	N/A	NP_001340973.1
	WDPCP	NM_001042692.3		c.1439-6C>T		splice_region intron	N/A	NP_001036157.1	O95876-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.1916-6C>T		splice_region intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000398544.7	TSL:1	c.1439-6C>T		splice_region intron	N/A	ENSP00000381552.3	O95876-3
	WDPCP	ENST00000409120.5	TSL:1	c.1340-6C>T		splice_region intron	N/A	ENSP00000386769.1	E9PFG9

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Bardet-Biedl syndrome 15 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;