rs141340867

Variant names:

• chr2-63588204-G-A
• rs141340867
• NM_015910.7:c.68C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-63588204-G-A
• chr2-63588204-G-C
• chr2-63588204-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354044.2(WDPCP):​c.-257C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000494 in 1,416,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: WDPCP NM_001354044.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.47
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048865378).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354044.2. 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.68C>T	p.Pro23Leu	missense	Exon 1 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.-257C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001340973.1
	WDPCP	NM_001354045.2		c.68C>T	p.Pro23Leu	missense	Exon 1 of 13	NP_001340974.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.68C>T	p.Pro23Leu	missense	Exon 1 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.68C>T	p.Pro23Leu	missense	Exon 1 of 14	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000409835.5	TSL:1	n.315C>T		non_coding_transcript_exon	Exon 1 of 13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000555 AC: 1 AN: 180074 AF XY: 0.0000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000137

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000494 AC: 7 AN: 1416468 Hom.: 0 Cov.: 31 AF XY: 0.00000571 AC XY: 4 AN XY: 700394

African (AFR) AF: 0.00 AC: 0 AN: 31942

American (AMR) AF: 0.00 AC: 0 AN: 40530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25440

East Asian (EAS) AF: 0.00 AC: 0 AN: 36666

South Asian (SAS) AF: 0.00 AC: 0 AN: 80906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000644 AC: 7 AN: 1086598

Other (OTH) AF: 0.00 AC: 0 AN: 58464

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000846 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.47
DANN	Benign	0.88
DEOGEN2	Benign	0.00055	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.088
Sift	Benign	0.15	T
Polyphen		0.055	B
Vest4		0.095
MutPred		0.15		Loss of loop (P = 0.0153)
MVP		0.22
MPC		0.11
ClinPred		0.049	T
GERP RS		-3.5
PromoterAI		0.0070	Neutral
Varity_R		0.024
gMVP		0.20
Mutation Taster		=100/0	polymorphism

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: rs141340867; hg19: chr2-63815338;