2-63121380-CTTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr2-63121380-CTT-C
• rs139878372
• NM_015910.7:c.*624_*625delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015910.7(WDPCP):​c.*624_*625delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 16 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (15190 hom., cov: 0)
  • Exomes 𝑓: 0.31 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100
• 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 -10 ACMG points.

• BP6: Variant 2-63121380-CTT-C is Benign according to our data. Variant chr2-63121380-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 369345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0976 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.*624_*625delAA		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*624_*625delAA		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*624_*625delAA		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.*624_*625delAA		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946853.1		c.*624_*625delAA		splice_region	Exon 14 of 14	ENSP00000616912.1
	WDPCP	ENST00000872046.1		c.*624_*625delAA		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 56505 AN: 88378 Hom.: 15193 Cov.: 0

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.647

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 0 AF XY: 0.286 AC XY: 4 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: 0.286 AC: 4 AN: 14

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.639 AC: 56493 AN: 88364 Hom.: 15190 Cov.: 0 AF XY: 0.649 AC XY: 26482 AN XY: 40828

African (AFR) AF: 0.627 AC: 14436 AN: 23028

American (AMR) AF: 0.718 AC: 5399 AN: 7520

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1396 AN: 2496

East Asian (EAS) AF: 0.758 AC: 2372 AN: 3128

South Asian (SAS) AF: 0.717 AC: 1758 AN: 2452

European-Finnish (FIN) AF: 0.712 AC: 1992 AN: 2798

Middle Eastern (MID) AF: 0.701 AC: 108 AN: 154

European-Non Finnish (NFE) AF: 0.620 AC: 27921 AN: 45068

Other (OTH) AF: 0.648 AC: 735 AN: 1134

Alfa AF: 0.385 Hom.: 481

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs139878372; hg19: chr2-63348515;