10-120858636-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018117.12(WDR11):c.199-7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,528 control chromosomes in the GnomAD database, including 31,384 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2432 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28952 hom. )

Consequence

WDR11
NM_018117.12 splice_region, intron

Scores

Splicing: ADA: 0.0003091

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.755

Publications

13 publications found

Variant links:

Genes affected

WDR11 (HGNC:13831): (WD repeat domain 11) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]

WDR11 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 14 with or without anosmia
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
intellectual developmental disorder, autosomal recessive 78
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WDR11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 10-120858636-G-C is Benign according to our data. Variant chr10-120858636-G-C is described in ClinVar as Benign. ClinVar VariationId is 1261179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018117.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	NM_018117.12	MANE Select	c.199-7G>C		splice_region intron	N/A	NP_060587.8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDR11	ENST00000263461.11	TSL:1 MANE Select	c.199-7G>C	splice_region intron	N/A	ENSP00000263461.5
WDR11	ENST00000497136.6	TSL:1	n.-579-7G>C	splice_region intron	N/A	ENSP00000474595.1
WDR11	ENST00000605543.5	TSL:2	n.166+6033G>C	intron	N/A	ENSP00000475076.1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23867

AN:

152092

Hom.:

2432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.209

AC:

52407

AN:

251202

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.0511

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.191

AC:

278442

AN:

1461318

Hom.:

28952

Cov.:

AF XY:

0.189

AC XY:

137048

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.0473

AC:

1583

AN:

33478

American (AMR)

AF:

0.382

AC:

17074

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

6572

AN:

26130

East Asian (EAS)

AF:

0.323

AC:

12800

AN:

39686

South Asian (SAS)

AF:

0.164

AC:

14134

AN:

86238

European-Finnish (FIN)

AF:

0.124

AC:

6600

AN:

53406

Middle Eastern (MID)

AF:

0.127

AC:

733

AN:

5768

European-Non Finnish (NFE)

AF:

0.187

AC:

207627

AN:

1111526

Other (OTH)

AF:

0.187

AC:

11319

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

11260

22521

33781

45042

56302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7536

15072

22608

30144

37680

<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:

0.157

AC:

23860

AN:

152210

Hom.:

2432

Cov.:

AF XY:

0.157

AC XY:

11685

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0547

AC:

2270

AN:

41534

American (AMR)

AF:

0.276

AC:

4225

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

792

AN:

3468

East Asian (EAS)

AF:

0.338

AC:

1744

AN:

5162

South Asian (SAS)

AF:

0.160

AC:

774

AN:

4830

European-Finnish (FIN)

AF:

0.118

AC:

1248

AN:

10608

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12319

AN:

68002

Other (OTH)

AF:

0.153

AC:

324

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

988

1976

2965

3953

4941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.180

Hom.:

899

Bravo

AF:

0.167

Asia WGS

AF:

0.245

AC:

854

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.171

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hypogonadotropic hypogonadism 14 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.5

(source)

DANN

Benign

0.88

PhyloP100

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.064

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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over