chr2-63121465-G-C

Variant names:

• chr2-63121465-G-C
• rs532612381
• NM_015910.7:c.*541C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_015910.7(WDPCP):​c.*541C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000988 in 141,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.708
• 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

ENSG00000286480 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000988 (14/141682) while in subpopulation EAS AF = 0.00274 (13/4752). AF 95% confidence interval is 0.00162. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*541C>G		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*541C>G		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*541C>G		3_prime_UTR	Exon 12 of 12	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.*541C>G		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946854.1		c.*541C>G		3_prime_UTR	Exon 19 of 19	ENSP00000616913.1
	WDPCP	ENST00000872046.1		c.*541C>G		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

Frequencies

GnomAD3 genomes AF: 0.0000989 AC: 14 AN: 141612 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000763

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00273

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 754 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 448

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 62

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 28

South Asian (SAS) AF: 0.00 AC: 0 AN: 40

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 586

Other (OTH) AF: 0.00 AC: 0 AN: 20

GnomAD4 genome AF: 0.0000988 AC: 14 AN: 141682 Hom.: 0 Cov.: 30 AF XY: 0.0000883 AC XY: 6 AN XY: 67988

African (AFR) AF: 0.00 AC: 0 AN: 38064

American (AMR) AF: 0.0000762 AC: 1 AN: 13118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00274 AC: 13 AN: 4752

South Asian (SAS) AF: 0.00 AC: 0 AN: 4450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66602

Other (OTH) AF: 0.00 AC: 0 AN: 1948

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000125

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bardet-Biedl syndrome 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		-0.71

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: rs532612381; hg19: chr2-63348600;