chr10-120852958-G-A

Variant names:

• chr10-120852958-G-A
• rs41287984
• NM_018117.12:c.198+323G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018117.12(WDR11):​c.198+323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,186 control chromosomes in the GnomAD database, including 2,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2145 hom., cov: 33)
• Consequence: WDR11 NM_018117.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.925
• Publications: 0 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: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• intellectual developmental disorder, autosomal recessive 78

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-120852958-G-A is Benign according to our data. Variant chr10-120852958-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	NM_018117.12	MANE Select	c.198+323G>A		intron	N/A	NP_060587.8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	ENST00000263461.11	TSL:1 MANE Select	c.198+323G>A		intron	N/A	ENSP00000263461.5	Q9BZH6
	WDR11	ENST00000497136.6	TSL:1	n.-580+323G>A		intron	N/A	ENSP00000474595.1	S4R3P9
	WDR11	ENST00000605543.5	TSL:2	n.166+355G>A		intron	N/A	ENSP00000475076.1	S4R451

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23232 AN: 152068 Hom.: 2140 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.153 AC: 23239 AN: 152186 Hom.: 2145 Cov.: 33 AF XY: 0.151 AC XY: 11263 AN XY: 74402

African (AFR) AF: 0.0701 AC: 2913 AN: 41544

American (AMR) AF: 0.139 AC: 2122 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5170

South Asian (SAS) AF: 0.136 AC: 654 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2071 AN: 10566

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13929 AN: 67992

Other (OTH) AF: 0.181 AC: 382 AN: 2116

Alfa AF: 0.173 Hom.: 331

Bravo AF: 0.144

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		0.93
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: rs41287984; hg19: chr10-122612470;