rs992214

Variant names:

• chr2-63259294-C-T
• rs992214
• NM_015910.7:c.1915+13G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-63259294-C-T
• chr2-63259294-C-A
• chr2-63259294-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_015910.7(WDPCP):​c.1915+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,600,990 control chromosomes in the GnomAD database, including 249,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (33809 hom., cov: 32)
  • Exomes 𝑓: 0.53 (215679 hom.)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.434
• Publications: 11 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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-63259294-C-T is Benign according to our data. Variant chr2-63259294-C-T is described in ClinVar as Benign. ClinVar VariationId is 95744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

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.1915+13G>A		intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.1843+13G>A		intron	N/A	NP_001340973.1
	WDPCP	NM_001042692.3		c.1438+13G>A		intron	N/A	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.1915+13G>A		intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.1813-29422G>A		intron	N/A	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000398544.7	TSL:1	c.1438+13G>A		intron	N/A	ENSP00000381552.3	O95876-3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97256 AN: 151910 Hom.: 33761 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.604 AC: 149498 AN: 247674 AF XY: 0.599

Gnomad AFR exome AF: 0.903

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.854

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.534 AC: 773420 AN: 1448962 Hom.: 215679 Cov.: 29 AF XY: 0.538 AC XY: 388183 AN XY: 721810

African (AFR) AF: 0.907 AC: 30154 AN: 33228

American (AMR) AF: 0.664 AC: 29660 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 17672 AN: 26014

East Asian (EAS) AF: 0.853 AC: 33678 AN: 39478

South Asian (SAS) AF: 0.721 AC: 61987 AN: 86004

European-Finnish (FIN) AF: 0.420 AC: 21851 AN: 52000

Middle Eastern (MID) AF: 0.672 AC: 3846 AN: 5726

European-Non Finnish (NFE) AF: 0.490 AC: 540027 AN: 1101888

Other (OTH) AF: 0.576 AC: 34545 AN: 59962

GnomAD4 genome AF: 0.640 AC: 97362 AN: 152028 Hom.: 33809 Cov.: 32 AF XY: 0.639 AC XY: 47469 AN XY: 74266

African (AFR) AF: 0.891 AC: 37018 AN: 41540

American (AMR) AF: 0.647 AC: 9874 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2414 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4404 AN: 5186

South Asian (SAS) AF: 0.722 AC: 3472 AN: 4812

European-Finnish (FIN) AF: 0.409 AC: 4295 AN: 10514

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33805 AN: 67940

Other (OTH) AF: 0.639 AC: 1344 AN: 2104

Alfa AF: 0.566 Hom.: 9413

Bravo AF: 0.667

Asia WGS AF: 0.799 AC: 2775 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Bardet-Biedl syndrome 1 (2)
-	-	2	Bardet-Biedl syndrome 15 (2)
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Heart defect - tongue hamartoma - polysyndactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.66
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs992214; hg19: chr2-63486429;