10-120851145-T-C

Variant names:

• chr10-120851145-T-C
• rs11199598
• ENST00000598981.5:n.65A>G

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.219A>G 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 0.319 in 536,662 control chromosomes in the GnomAD database, including 28,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6872 hom., cov: 34)
  • Exomes 𝑓: 0.33 (21717 hom.)
• Consequence: WDR11-DT ENST00000628194.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550
• Publications: 11 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=-0.79).
• BP6: Variant 10-120851145-T-C is Benign according to our data. Variant chr10-120851145-T-C is described in ClinVar as Benign. ClinVar VariationId is 1261778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 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.35A>G		non_coding_transcript_exon	Exon 1 of 3
	WDR11	NM_018117.12	MANE Select	c.-276T>C		upstream_gene	N/A	NP_060587.8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11-DT	ENST00000598981.5	TSL:5	n.65A>G		non_coding_transcript_exon	Exon 1 of 4
	WDR11-DT	ENST00000628194.3	TSL:2	n.219A>G		non_coding_transcript_exon	Exon 1 of 3
	WDR11-DT	ENST00000630905.5	TSL:2	n.313A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43767 AN: 152068 Hom.: 6870 Cov.: 34

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.331 AC: 127175 AN: 384476 Hom.: 21717 Cov.: 2 AF XY: 0.330 AC XY: 66597 AN XY: 201624

African (AFR) AF: 0.145 AC: 1567 AN: 10818

American (AMR) AF: 0.448 AC: 7161 AN: 15992

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 4675 AN: 11894

East Asian (EAS) AF: 0.365 AC: 9403 AN: 25740

South Asian (SAS) AF: 0.327 AC: 13447 AN: 41162

European-Finnish (FIN) AF: 0.291 AC: 6940 AN: 23874

Middle Eastern (MID) AF: 0.313 AC: 524 AN: 1672

European-Non Finnish (NFE) AF: 0.330 AC: 76113 AN: 230930

Other (OTH) AF: 0.328 AC: 7345 AN: 22394

GnomAD4 genome AF: 0.288 AC: 43773 AN: 152186 Hom.: 6872 Cov.: 34 AF XY: 0.288 AC XY: 21394 AN XY: 74400

African (AFR) AF: 0.145 AC: 6026 AN: 41556

American (AMR) AF: 0.405 AC: 6189 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1982 AN: 5164

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4818

European-Finnish (FIN) AF: 0.281 AC: 2971 AN: 10584

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22636 AN: 67980

Other (OTH) AF: 0.297 AC: 627 AN: 2114

Alfa AF: 0.316 Hom.: 10058

Bravo AF: 0.292

Asia WGS AF: 0.342 AC: 1191 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	-0.79
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		-0.055
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11199598; hg19: chr10-122610657;