2-63121679-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015910.7(WDPCP):c.*327G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 367,680 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (11 hom.)
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-63121679-C-T is Benign according to our data. Variant chr2-63121679-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 895794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00148 (225/152082) while in subpopulation SAS AF= 0.0203 (98/4818). AF 95% confidence interval is 0.0171. There are 2 homozygotes in gnomad4. There are 141 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDPCP	NM_015910.7	c.*327G>A		3_prime_UTR_variant	18/18	ENST00000272321.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDPCP	ENST00000272321.12	c.*327G>A		3_prime_UTR_variant	18/18	1	NM_015910.7	P1
	ENST00000657946.1	n.130+14671C>T		intron_variant, non_coding_transcript_variant
WDPCP	ENST00000409199.5	c.*327G>A		3_prime_UTR_variant	12/12	2
WDPCP	ENST00000409354.6	c.*617G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 226 AN: 151960 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00267 AC: 576 AN: 215598 Hom.: 11 Cov.: 5 AF XY: 0.00349 AC XY: 387 AN XY: 111002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.000257

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0183

Gnomad4 FIN exome AF: 0.000154

Gnomad4 NFE exome AF: 0.00135

Gnomad4 OTH exome AF: 0.00298

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152082 Hom.: 2 Cov.: 31 AF XY: 0.00190 AC XY: 141 AN XY: 74328

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.000473

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.000967

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bardet-Biedl syndrome 15 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.1
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs565212301; hg19: chr2-63348814;