2-63121380-CTTTTTTTTTTTTTT-CTTTTTTTTTTT

Variant names:

• chr2-63121380-CTTT-C
• rs139878372
• NM_015910.7:c.*623_*625delAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_015910.7(WDPCP):​c.*623_*625delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 16 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.19 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.188 (3/16) while in subpopulation NFE AF = 0.143 (2/14). AF 95% confidence interval is 0.0254. There are 0 homozygotes in GnomAdExome4. There are 3 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

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.*623_*625delAAA		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*623_*625delAAA		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*623_*625delAAA		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.*623_*625delAAA		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946853.1		c.*623_*625delAAA		splice_region	Exon 14 of 14	ENSP00000616912.1
	WDPCP	ENST00000872046.1		c.*623_*625delAAA		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 310 AN: 87318 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00389

Gnomad ASJ AF: 0.000405

Gnomad EAS AF: 0.00352

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00144

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00180

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.143 AC: 2 AN: 14

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00355 AC: 310 AN: 87306 Hom.: 0 Cov.: 0 AF XY: 0.00387 AC XY: 156 AN XY: 40348

African (AFR) AF: 0.00935 AC: 214 AN: 22888

American (AMR) AF: 0.00389 AC: 29 AN: 7456

Ashkenazi Jewish (ASJ) AF: 0.000405 AC: 1 AN: 2472

East Asian (EAS) AF: 0.00353 AC: 11 AN: 3114

South Asian (SAS) AF: 0.00 AC: 0 AN: 2438

European-Finnish (FIN) AF: 0.00144 AC: 4 AN: 2776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 156

European-Non Finnish (NFE) AF: 0.00111 AC: 49 AN: 44310

Other (OTH) AF: 0.00179 AC: 2 AN: 1118

Alfa AF: 0.00 Hom.: 481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs139878372; hg19: chr2-63348515;