rs55807617

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.84).
• BP6: Variant 2-63121811-C-T is Benign according to our data. Variant chr2-63121811-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.*195G>A		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*195G>A		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*195G>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.*195G>A		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946854.1		c.*195G>A		3_prime_UTR	Exon 19 of 19	ENSP00000616913.1
	WDPCP	ENST00000872046.1		c.*195G>A		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

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

African (AFR) AF: 0.0930 AC: 2404 AN: 25856

American (AMR) AF: 0.00615 AC: 95 AN: 15444

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 435 AN: 16704

East Asian (EAS) AF: 0.00 AC: 0 AN: 32382

South Asian (SAS) AF: 0.000394 AC: 16 AN: 40588

European-Finnish (FIN) AF: 0.0000249 AC: 1 AN: 40150

Middle Eastern (MID) AF: 0.00713 AC: 23 AN: 3224

European-Non Finnish (NFE) AF: 0.000201 AC: 191 AN: 948778

Other (OTH) AF: 0.00851 AC: 409 AN: 48036

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

African (AFR) AF: 0.0895 AC: 3717 AN: 41526

American (AMR) AF: 0.0124 AC: 190 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68018

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.0140 Hom.: 37

Bravo AF: 0.0309

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.84
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.52
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: rs55807617; hg19: chr2-63348946;