10-120869576-C-G

Variant names:

• chr10-120869576-C-G
• rs7082695
• NM_018117.12:c.1295-1594C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018117.12(WDR11):​c.1295-1594C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,890 control chromosomes in the GnomAD database, including 10,615 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 0.37 (10615 hom., cov: 32)
• Consequence: WDR11 NM_018117.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.1295-1594C>G		intron_variant	Intron 9 of 28	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.1295-1594C>G		intron_variant	Intron 9 of 28	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000497136.6	n.414-1594C>G		intron_variant	Intron 7 of 25	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.167-1659C>G		intron_variant	Intron 2 of 21	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56505 AN: 151772 Hom.: 10602 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.372 AC: 56556 AN: 151890 Hom.: 10615 Cov.: 32 AF XY: 0.370 AC XY: 27466 AN XY: 74238

African (AFR) AF: 0.426 AC: 17640 AN: 41432

American (AMR) AF: 0.439 AC: 6706 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2150 AN: 5152

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 2990 AN: 10532

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22919 AN: 67906

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.353 Hom.: 1168

Bravo AF: 0.388

Asia WGS AF: 0.385 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		1.8
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: rs7082695; hg19: chr10-122629088;