10-120852260-A-T

Variant names:

• chr10-120852260-A-T
• rs7917351
• NM_018117.12:c.87-264A>T

Variant summary

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

The NM_018117.12(WDR11):​c.87-264A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 423,394 control chromosomes in the GnomAD database, including 13,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6230 hom., cov: 32)
  • Exomes 𝑓: 0.23 (7693 hom.)
• Consequence: WDR11 NM_018117.12 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-120852260-A-T is Benign according to our data. Variant chr10-120852260-A-T is described in ClinVar as [Benign]. Clinvar id is 1287118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.87-264A>T		intron_variant	Intron 1 of 28	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.87-264A>T		intron_variant	Intron 1 of 28	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.87-264A>T		intron_variant	Intron 1 of 21	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41030 AN: 151956 Hom.: 6214 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.228 AC: 61938 AN: 271320 Hom.: 7693 Cov.: 2 AF XY: 0.229 AC XY: 33573 AN XY: 146288

African (AFR) AF: 0.406 AC: 3269 AN: 8048

American (AMR) AF: 0.156 AC: 1878 AN: 12034

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 2048 AN: 7712

East Asian (EAS) AF: 0.105 AC: 1582 AN: 15048

South Asian (SAS) AF: 0.235 AC: 9395 AN: 39982

European-Finnish (FIN) AF: 0.222 AC: 2754 AN: 12396

Middle Eastern (MID) AF: 0.268 AC: 297 AN: 1110

European-Non Finnish (NFE) AF: 0.233 AC: 37232 AN: 160136

Other (OTH) AF: 0.234 AC: 3483 AN: 14854

GnomAD4 genome AF: 0.270 AC: 41083 AN: 152074 Hom.: 6230 Cov.: 32 AF XY: 0.263 AC XY: 19579 AN XY: 74342

African (AFR) AF: 0.404 AC: 16743 AN: 41452

American (AMR) AF: 0.193 AC: 2943 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.0994 AC: 514 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1105 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2142 AN: 10582

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15724 AN: 67988

Other (OTH) AF: 0.273 AC: 575 AN: 2110

Alfa AF: 0.254 Hom.: 654

Bravo AF: 0.275

Asia WGS AF: 0.167 AC: 583 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.43
PhyloP100		-1.7
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: rs7917351; hg19: chr10-122611772;