NM_015910.7:c.*327G>A

Variant names:

• chr2-63121679-C-T
• rs565212301
• NM_015910.7:c.*327G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.305
• 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: Benign. The variant received -20 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 VariationId is 895794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.*327G>A		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*327G>A		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*327G>A		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.*327G>A		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946854.1		c.*327G>A		3_prime_UTR	Exon 19 of 19	ENSP00000616913.1
	WDPCP	ENST00000872046.1		c.*327G>A		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

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

African (AFR) AF: 0.00 AC: 0 AN: 5042

American (AMR) AF: 0.00109 AC: 6 AN: 5524

Ashkenazi Jewish (ASJ) AF: 0.000257 AC: 1 AN: 3888

East Asian (EAS) AF: 0.00 AC: 0 AN: 7222

South Asian (SAS) AF: 0.0183 AC: 323 AN: 17696

European-Finnish (FIN) AF: 0.000154 AC: 1 AN: 6514

Middle Eastern (MID) AF: 0.00160 AC: 1 AN: 624

European-Non Finnish (NFE) AF: 0.00135 AC: 215 AN: 159370

Other (OTH) AF: 0.00298 AC: 29 AN: 9718

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

African (AFR) AF: 0.000289 AC: 12 AN: 41502

American (AMR) AF: 0.000786 AC: 12 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4818

European-Finnish (FIN) AF: 0.000473 AC: 5 AN: 10566

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 67974

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.000967

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 15 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.41
PhyloP100		0.30

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: rs565212301; hg19: chr2-63348814;