2-63527141-T-C

Variant names:

• chr2-63527141-T-C
• rs2421954
• NM_015910.7:c.76-34201A>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.76-34201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,040 control chromosomes in the GnomAD database, including 6,273 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 0.27 (6273 hom., cov: 32)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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.76-34201A>G		intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.4-34201A>G		intron	N/A	NP_001340973.1
	WDPCP	NM_001354045.2		c.76-34201A>G		intron	N/A	NP_001340974.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.76-34201A>G		intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.76-34201A>G		intron	N/A	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000409835.5	TSL:1	n.323-34201A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40309 AN: 151924 Hom.: 6255 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.265 AC: 40362 AN: 152040 Hom.: 6273 Cov.: 32 AF XY: 0.271 AC XY: 20117 AN XY: 74304

African (AFR) AF: 0.220 AC: 9102 AN: 41464

American (AMR) AF: 0.348 AC: 5313 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3727 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4814

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10564

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 16030 AN: 67976

Other (OTH) AF: 0.268 AC: 566 AN: 2112

Alfa AF: 0.254 Hom.: 21426

Bravo AF: 0.275

Asia WGS AF: 0.559 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.81
PhyloP100		0.40
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: rs2421954; hg19: chr2-63754275;