Genetic Variant WDPCP:c.1813-27A>G (chr2-63259436-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_015910.7(WDPCP):c.1813-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,577,392 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: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

WDPCP
NM_015910.7 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

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, G2P, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
heart defect - tongue hamartoma - polysyndactyly syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDPCP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000336 (479/1425108) while in subpopulation AMR AF = 0.00251 (112/44616). AF 95% confidence interval is 0.00213. There are 0 homozygotes in GnomAdExome4. There are 222 alleles in the male GnomAdExome4 subpopulation. Median coverage is 24. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDPCP	NM_015910.7	MANE Select	c.1813-27A>G	intron	N/A	NP_056994.3
WDPCP	NM_001354044.2		c.1741-27A>G	intron	N/A	NP_001340973.1
WDPCP	NM_001042692.3		c.1336-27A>G	intron	N/A	NP_001036157.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.1813-27A>G	intron	N/A	ENSP00000272321.7
WDPCP	ENST00000409562.7	TSL:1	c.1813-29564A>G	intron	N/A	ENSP00000387222.3
WDPCP	ENST00000398544.7	TSL:1	c.1336-27A>G	intron	N/A	ENSP00000381552.3

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000667

AC:

162

AN:

243028

AF XY:

0.000491

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000374

Gnomad OTH exome

AF:

0.00436

GnomAD4 exome

AF:

0.000336

AC:

479

AN:

1425108

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

222

AN XY:

711268

show subpopulations

African (AFR)

AF:

0.000274

AC:

AN:

32796

American (AMR)

AF:

0.00251

AC:

112

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0000772

AC:

AN:

25906

East Asian (EAS)

AF:

0.000127

AC:

AN:

39384

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46564

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.000287

AC:

311

AN:

1085290

Other (OTH)

AF:

0.000540

AC:

AN:

59286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000302

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41568

American (AMR)

AF:

0.000981

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68010

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000179

Hom.:

Bravo

AF:

0.000536

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over