chr2-63121683-T-C

Variant names:

• chr2-63121683-T-C
• rs369149310
• NM_015910.7:c.*323A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015910.7(WDPCP):​c.*323A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 390,016 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: WDPCP NM_015910.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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

ENSG00000286480 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-63121683-T-C is Benign according to our data. Variant chr2-63121683-T-C is described in ClinVar as Benign. ClinVar VariationId is 336753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00153 (233/152244) while in subpopulation SAS AF = 0.0475 (229/4826). AF 95% confidence interval is 0.0424. There are 9 homozygotes in GnomAd4. There are 180 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.*323A>G		3_prime_UTR	Exon 18 of 18	NP_056994.3	O95876-1
	WDPCP	NM_001354044.2		c.*323A>G		3_prime_UTR	Exon 19 of 19	NP_001340973.1
	WDPCP	NM_001042692.3		c.*323A>G		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.*323A>G		3_prime_UTR	Exon 18 of 18	ENSP00000272321.7	O95876-1
	WDPCP	ENST00000946854.1		c.*323A>G		3_prime_UTR	Exon 19 of 19	ENSP00000616913.1
	WDPCP	ENST00000872046.1		c.*323A>G		3_prime_UTR	Exon 18 of 18	ENSP00000542105.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152126 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00301 AC: 716 AN: 237772 Hom.: 13 Cov.: 5 AF XY: 0.00451 AC XY: 550 AN XY: 121844

African (AFR) AF: 0.00 AC: 0 AN: 5550

American (AMR) AF: 0.000353 AC: 2 AN: 5668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4154

East Asian (EAS) AF: 0.000789 AC: 6 AN: 7604

South Asian (SAS) AF: 0.0372 AC: 675 AN: 18156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 666

European-Non Finnish (NFE) AF: 0.0000168 AC: 3 AN: 178624

Other (OTH) AF: 0.00287 AC: 30 AN: 10468

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152244 Hom.: 9 Cov.: 31 AF XY: 0.00242 AC XY: 180 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000485 Hom.: 0

Bravo AF: 0.000249

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		2.0
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: rs369149310; hg19: chr2-63348818;