2-63121683-T-C

Position:

• chr2-63121683-T-C

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.*323A>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 0.00243 in 390,016 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98

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=-0.85).
• BP6: Variant 2-63121683-T-C is Benign according to our data. Variant chr2-63121683-T-C is described in ClinVar as [Benign]. Clinvar id is 336753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00153 (233/152244) while in subpopulation SAS AF= 0.0475 (229/4826). AF 95% confidence interval is 0.0424. There are 9 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.*323A>G		3_prime_UTR_variant	18/18	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12	c.*323A>G		3_prime_UTR_variant	18/18	1	NM_015910.7	ENSP00000272321	P1
	ENST00000657946.1	n.130+14675T>C		intron_variant, non_coding_transcript_variant
WDPCP	ENST00000409199.5	c.*323A>G		3_prime_UTR_variant	12/12	2		ENSP00000386592
WDPCP	ENST00000409354.6	c.*613A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000386795

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152126 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00301 AC: 716 AN: 237772 Hom.: 13 Cov.: 5 AF XY: 0.00451 AC XY: 550 AN XY: 121844

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000353

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000789

Gnomad4 SAS exome AF: 0.0372

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000168

Gnomad4 OTH exome AF: 0.00287

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152244 Hom.: 9 Cov.: 31 AF XY: 0.00242 AC XY: 180 AN XY: 74444

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000485 Hom.: 0

Bravo AF: 0.000249

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bardet-Biedl syndrome 15 Benign:1

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.66

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: rs369149310; hg19: chr2-63348818;