ENST00000630905.5:n.188T>C

Variant names:

• chr10-120851270-A-G
• rs78953227
• ENST00000628194.3:n.94T>C

Variant summary

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

The ENST00000630905.5(WDR11-DT):​n.188T>C 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 0.00796 in 704,304 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (196 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (48 hom.)
• Consequence: WDR11-DT ENST00000630905.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.429
• Publications: 0 publications found

Genes affected

WDR11-DT (HGNC:27437): (WDR11 divergent transcript)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-120851270-A-G is Benign according to our data. Variant chr10-120851270-A-G is described in ClinVar as Benign. ClinVar VariationId is 1232088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000630905.5. 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.-151A>G		upstream_gene	N/A	NP_060587.8
	WDR11-DT	NR_033850.1		n.-91T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11-DT	ENST00000628194.3	TSL:2	n.94T>C		non_coding_transcript_exon	Exon 1 of 3
	WDR11-DT	ENST00000630905.5	TSL:2	n.188T>C		non_coding_transcript_exon	Exon 1 of 3
	WDR11	ENST00000263461.11	TSL:1 MANE Select	c.-151A>G		upstream_gene	N/A	ENSP00000263461.5	Q9BZH6

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3903 AN: 152224 Hom.: 196 Cov.: 33

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.00308 AC: 1701 AN: 551962 Hom.: 48 Cov.: 7 AF XY: 0.00254 AC XY: 747 AN XY: 294104

African (AFR) AF: 0.0871 AC: 1301 AN: 14940

American (AMR) AF: 0.00554 AC: 157 AN: 28356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17142

East Asian (EAS) AF: 0.00 AC: 0 AN: 31858

South Asian (SAS) AF: 0.000198 AC: 11 AN: 55684

European-Finnish (FIN) AF: 0.0000293 AC: 1 AN: 34172

Middle Eastern (MID) AF: 0.00129 AC: 3 AN: 2324

European-Non Finnish (NFE) AF: 0.000142 AC: 48 AN: 337730

Other (OTH) AF: 0.00605 AC: 180 AN: 29756

GnomAD4 genome AF: 0.0257 AC: 3908 AN: 152342 Hom.: 196 Cov.: 33 AF XY: 0.0253 AC XY: 1881 AN XY: 74490

African (AFR) AF: 0.0898 AC: 3734 AN: 41574

American (AMR) AF: 0.00817 AC: 125 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68038

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0217 Hom.: 11

Bravo AF: 0.0291

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.43
PromoterAI		-0.069	Neutral
Mutation Taster		=300/0	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: rs78953227; hg19: chr10-122610782;