10-120851127-T-G

Variant names:

• chr10-120851127-T-G
• rs12778011
• ENST00000456120.6:n.18A>C

Variant summary

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

The ENST00000628194.3(WDR11-DT):​n.237A>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 0.136 in 505,340 control chromosomes in the GnomAD database, including 5,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1318 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3847 hom.)
• Consequence: WDR11-DT ENST00000628194.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.679
• Publications: 3 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, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-120851127-T-G is Benign according to our data. Variant chr10-120851127-T-G is described in ClinVar as Benign. ClinVar VariationId is 1289331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000628194.3. 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-DT	NR_033850.1		n.53A>C		non_coding_transcript_exon	Exon 1 of 3
	WDR11	NM_018117.12	MANE Select	c.-294T>G		upstream_gene	N/A	NP_060587.8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11-DT	ENST00000456120.6	TSL:5	n.18A>C		non_coding_transcript_exon	Exon 1 of 4
	WDR11-DT	ENST00000598981.5	TSL:5	n.83A>C		non_coding_transcript_exon	Exon 1 of 4
	WDR11-DT	ENST00000628194.3	TSL:2	n.237A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19294 AN: 152150 Hom.: 1315 Cov.: 33

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.140 AC: 49393 AN: 353072 Hom.: 3847 Cov.: 0 AF XY: 0.141 AC XY: 26243 AN XY: 185656

African (AFR) AF: 0.0813 AC: 828 AN: 10186

American (AMR) AF: 0.104 AC: 1546 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 1797 AN: 10960

East Asian (EAS) AF: 0.0251 AC: 566 AN: 22520

South Asian (SAS) AF: 0.163 AC: 6635 AN: 40706

European-Finnish (FIN) AF: 0.165 AC: 3408 AN: 20608

Middle Eastern (MID) AF: 0.178 AC: 269 AN: 1508

European-Non Finnish (NFE) AF: 0.149 AC: 31378 AN: 211094

Other (OTH) AF: 0.144 AC: 2966 AN: 20580

GnomAD4 genome AF: 0.127 AC: 19303 AN: 152268 Hom.: 1318 Cov.: 33 AF XY: 0.127 AC XY: 9441 AN XY: 74442

African (AFR) AF: 0.0794 AC: 3302 AN: 41562

American (AMR) AF: 0.126 AC: 1927 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3468

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5184

South Asian (SAS) AF: 0.171 AC: 824 AN: 4830

European-Finnish (FIN) AF: 0.163 AC: 1732 AN: 10594

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10228 AN: 68012

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.136 Hom.: 3500

Bravo AF: 0.120

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.59
CADD	Benign	5.5
DANN	Benign	0.84
PhyloP100		-0.68
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12778011; hg19: chr10-122610639;