2-63284300-G-T

Variant names:

• chr2-63284300-G-T
• rs2138798
• NM_015910.7:c.1813-24891C>A

Variant summary

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

The NM_015910.7(WDPCP):​c.1813-24891C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,036 control chromosomes in the GnomAD database, including 3,785 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 0.20 (3785 hom., cov: 32)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.1813-24891C>A		intron_variant	Intron 13 of 17	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12	c.1813-24891C>A		intron_variant	Intron 13 of 17	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30144 AN: 151918 Hom.: 3781 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.198 AC: 30175 AN: 152036 Hom.: 3785 Cov.: 32 AF XY: 0.201 AC XY: 14965 AN XY: 74310

African (AFR) AF: 0.257 AC: 10676 AN: 41486

American (AMR) AF: 0.178 AC: 2718 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3106 AN: 5164

South Asian (SAS) AF: 0.365 AC: 1756 AN: 4806

European-Finnish (FIN) AF: 0.107 AC: 1126 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9578 AN: 67948

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.168 Hom.: 2854

Bravo AF: 0.203

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.39
PhyloP100		-0.51
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: rs2138798; hg19: chr2-63511435;