2-63487493-ATC-GTT

Variant names:

• chr2-63487493-ATC-GTT
• NM_015910.7:c.161-1_162delGATinsAAC
• WDPCP p.55

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_015910.7(WDPCP):​c.161-1_162delGATinsAAC​(p.55) variant causes a splice acceptor, splice region, synonymous, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDPCP NM_015910.7 splice_acceptor, splice_region, synonymous, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.02141901 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.8, offset of 4, new splice context is: ttcttcctttctataaacAGaga. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

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.161-1_162delGATinsAAC	p.55	splice_acceptor splice_region synonymous intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.89-1_90delGATinsAAC	p.31	splice_acceptor splice_region synonymous intron	N/A	NP_001340973.1
	WDPCP	NM_001354045.2		c.161-1_162delGATinsAAC	p.55	splice_acceptor splice_region synonymous intron	N/A	NP_001340974.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.161-1_162delGATinsAAC	p.55	splice_acceptor splice_region synonymous intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.161-1_162delGATinsAAC	p.55	splice_acceptor splice_region synonymous intron	N/A	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000409835.5	TSL:1	n.408-1_409delGATinsAAC		splice_acceptor splice_region intron non_coding_transcript_exon	Exon 3 of 13

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4

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

hg19: chr2-63714627;