2-63439737-T-C

Variant names:

• chr2-63439737-T-C
• rs186575824
• NM_015910.7:c.499+20A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS1

The NM_015910.7(WDPCP):​c.499+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,604,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: WDPCP NM_015910.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.11
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 2-63439737-T-C is Benign according to our data. Variant chr2-63439737-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00153 (233/152108) while in subpopulation AFR AF = 0.00516 (214/41502). AF 95% confidence interval is 0.00459. There are 0 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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.499+20A>G		intron	N/A	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.427+20A>G		intron	N/A	NP_001340973.1
	WDPCP	NM_001354045.2		c.499+20A>G		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.499+20A>G		intron	N/A	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000409562.7	TSL:1	c.499+20A>G		intron	N/A	ENSP00000387222.3	O95876-2
	WDPCP	ENST00000409120.5	TSL:1	c.-78+20A>G		intron	N/A	ENSP00000386769.1	E9PFG9

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000305 AC: 76 AN: 248968 AF XY: 0.000244

Gnomad AFR exome AF: 0.00414

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000123 AC: 178 AN: 1452864 Hom.: 1 Cov.: 27 AF XY: 0.000116 AC XY: 84 AN XY: 723434

African (AFR) AF: 0.00427 AC: 142 AN: 33282

American (AMR) AF: 0.000314 AC: 14 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104042

Other (OTH) AF: 0.000316 AC: 19 AN: 60042

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74364

African (AFR) AF: 0.00516 AC: 214 AN: 41502

American (AMR) AF: 0.000983 AC: 15 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.0000856 Hom.: 0

Bravo AF: 0.00142

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs186575824; hg19: chr2-63666871;