chr2-63121811-C-T

Variant names:

• chr2-63121811-C-T
• rs55807617
• NM_015910.7:c.*195G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015910.7(WDPCP):​c.*195G>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 0.00579 in 1,323,414 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (168 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (129 hom.)
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.521

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]

ENSG00000286480 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-63121811-C-T is Benign according to our data. Variant chr2-63121811-C-T is described in ClinVar as [Benign]. Clinvar id is 336754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.*195G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321	c.*195G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4075 AN: 152134 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.00305 AC: 3574 AN: 1171162 Hom.: 129 Cov.: 17 AF XY: 0.00285 AC XY: 1607 AN XY: 564646

Gnomad4 AFR exome AF: 0.0930

Gnomad4 AMR exome AF: 0.00615

Gnomad4 ASJ exome AF: 0.0260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000249

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00851

GnomAD4 genome AF: 0.0269 AC: 4093 AN: 152252 Hom.: 168 Cov.: 32 AF XY: 0.0260 AC XY: 1939 AN XY: 74440

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0142 Hom.: 21

Bravo AF: 0.0309

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bardet-Biedl syndrome 15 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.62

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: rs55807617; hg19: chr2-63348946;