2-63814810-T-C

Variant names:

• chr2-63814810-T-C
• rs10201844
• XM_047444626.1:c.-4902-1103A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000816213.1(ENSG00000289943):​n.751+25233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,154 control chromosomes in the GnomAD database, including 4,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4954 hom., cov: 32)
• Consequence: ENSG00000289943 ENST00000816213.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888
• Publications: 2 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

ENSG00000289943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000816213.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDPCP	ENST00000467687.1	TSL:5	n.223-1103A>G		intron	N/A
	WDPCP	ENST00000490935.5	TSL:5	n.223-1103A>G		intron	N/A
	ENSG00000289943	ENST00000816213.1		n.751+25233A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33368 AN: 152036 Hom.: 4954 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.219 AC: 33394 AN: 152154 Hom.: 4954 Cov.: 32 AF XY: 0.225 AC XY: 16734 AN XY: 74382

African (AFR) AF: 0.111 AC: 4596 AN: 41560

American (AMR) AF: 0.294 AC: 4488 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3924 AN: 5176

South Asian (SAS) AF: 0.388 AC: 1873 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2429 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14452 AN: 67958

Other (OTH) AF: 0.226 AC: 478 AN: 2114

Alfa AF: 0.218 Hom.: 11227

Bravo AF: 0.223

Asia WGS AF: 0.569 AC: 1973 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		0.89

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

dbSNP: rs10201844;

hg19: chr2-64041944;