rs10886800

Variant names:

• chr10-120908900-G-A
• rs10886800
• ENST00000497136.6:n.*3135G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000497136.6(WDR11):​n.*3135G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 645,812 control chromosomes in the GnomAD database, including 12,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2435 hom., cov: 33)
  • Exomes 𝑓: 0.19 (10067 hom.)
• Consequence: WDR11 ENST00000497136.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353
• Publications: 11 publications found

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

LOC105378519 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-120908900-G-A is Benign according to our data. Variant chr10-120908900-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.*187G>A		3_prime_UTR_variant	Exon 29 of 29	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000497136.6	n.*3135G>A		non_coding_transcript_exon_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2381G>A		non_coding_transcript_exon_variant	Exon 22 of 22	2		ENSP00000475076.1
WDR11	ENST00000263461.11	c.*187G>A		3_prime_UTR_variant	Exon 29 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000497136.6	n.*3135G>A		3_prime_UTR_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2381G>A		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23871 AN: 152068 Hom.: 2435 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.190 AC: 93840 AN: 493626 Hom.: 10067 Cov.: 6 AF XY: 0.188 AC XY: 49327 AN XY: 262582

African (AFR) AF: 0.0542 AC: 726 AN: 13404

American (AMR) AF: 0.352 AC: 8110 AN: 23022

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 3878 AN: 15524

East Asian (EAS) AF: 0.318 AC: 9887 AN: 31054

South Asian (SAS) AF: 0.163 AC: 8155 AN: 50106

European-Finnish (FIN) AF: 0.128 AC: 4054 AN: 31738

Middle Eastern (MID) AF: 0.132 AC: 277 AN: 2100

European-Non Finnish (NFE) AF: 0.179 AC: 53686 AN: 299114

Other (OTH) AF: 0.184 AC: 5067 AN: 27564

GnomAD4 genome AF: 0.157 AC: 23865 AN: 152186 Hom.: 2435 Cov.: 33 AF XY: 0.157 AC XY: 11683 AN XY: 74394

African (AFR) AF: 0.0548 AC: 2279 AN: 41550

American (AMR) AF: 0.276 AC: 4225 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1741 AN: 5158

South Asian (SAS) AF: 0.160 AC: 770 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1243 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12328 AN: 67996

Other (OTH) AF: 0.152 AC: 322 AN: 2112

Alfa AF: 0.189 Hom.: 1653

Bravo AF: 0.167

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.56
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10886800; hg19: chr10-122668412;