rs1850983

Variant names:

• chr2-63221589-G-C
• rs1850983
• NM_015910.7:c.1915+37718C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015910.7(WDPCP):​c.1915+37718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,276 control chromosomes in the GnomAD database, including 67,810 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67810 hom., cov: 32)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.969 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.1915+37718C>G		intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.1843+37718C>G		intron	N/A	NP_001340973.1
	WDPCP	NM_001042692.3		c.1438+37718C>G		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.1915+37718C>G		intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000398544.7	TSL:1	c.1438+37718C>G		intron	N/A	ENSP00000381552.3	O95876-3
	WDPCP	ENST00000409120.5	TSL:1	c.1339+37718C>G		intron	N/A	ENSP00000386769.1	E9PFG9

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143366 AN: 152158 Hom.: 67756 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.949

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.942 AC: 143479 AN: 152276 Hom.: 67810 Cov.: 32 AF XY: 0.943 AC XY: 70258 AN XY: 74468

African (AFR) AF: 0.866 AC: 35985 AN: 41532

American (AMR) AF: 0.968 AC: 14806 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3218 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4770 AN: 5188

South Asian (SAS) AF: 0.990 AC: 4773 AN: 4822

European-Finnish (FIN) AF: 0.977 AC: 10373 AN: 10622

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.975 AC: 66343 AN: 68032

Other (OTH) AF: 0.950 AC: 2008 AN: 2114

Alfa AF: 0.959 Hom.: 8704

Bravo AF: 0.937

Asia WGS AF: 0.964 AC: 3353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.35
PhyloP100		0.32
Mutation Taster		=100/0	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: rs1850983; hg19: chr2-63448724;