rs7077126

Variant names:

• chr10-120908784-G-A
• rs7077126
• ENST00000497136.6:n.*3019G>A

Variant summary

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

The ENST00000497136.6(WDR11):​n.*3019G>A 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 0.352 in 1,556,868 control chromosomes in the GnomAD database, including 98,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11077 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87333 hom.)
• Consequence: WDR11 ENST00000497136.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365
• Publications: 12 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

LOC105378519 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-120908784-G-A is Benign according to our data. Variant chr10-120908784-G-A is described in ClinVar as [Benign]. Clinvar id is 1231652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.*71G>A		3_prime_UTR_variant	Exon 29 of 29	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000497136.6	n.*3019G>A		non_coding_transcript_exon_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2265G>A		non_coding_transcript_exon_variant	Exon 22 of 22	2		ENSP00000475076.1
WDR11	ENST00000263461.11	c.*71G>A		3_prime_UTR_variant	Exon 29 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000497136.6	n.*3019G>A		3_prime_UTR_variant	Exon 26 of 26	1		ENSP00000474595.1
WDR11	ENST00000605543.5	n.*2265G>A		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57516 AN: 151792 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.349 AC: 490380 AN: 1404958 Hom.: 87333 Cov.: 23 AF XY: 0.346 AC XY: 243118 AN XY: 702492

African (AFR) AF: 0.439 AC: 14181 AN: 32310

American (AMR) AF: 0.519 AC: 23087 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10501 AN: 25804

East Asian (EAS) AF: 0.386 AC: 15212 AN: 39418

South Asian (SAS) AF: 0.323 AC: 27416 AN: 84990

European-Finnish (FIN) AF: 0.292 AC: 15292 AN: 52414

Middle Eastern (MID) AF: 0.344 AC: 1436 AN: 4178

European-Non Finnish (NFE) AF: 0.341 AC: 362283 AN: 1062942

Other (OTH) AF: 0.359 AC: 20972 AN: 58388

GnomAD4 genome AF: 0.379 AC: 57572 AN: 151910 Hom.: 11077 Cov.: 32 AF XY: 0.376 AC XY: 27955 AN XY: 74258

African (AFR) AF: 0.450 AC: 18606 AN: 41384

American (AMR) AF: 0.441 AC: 6729 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3466

East Asian (EAS) AF: 0.417 AC: 2139 AN: 5134

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

European-Finnish (FIN) AF: 0.283 AC: 2988 AN: 10564

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

European-Non Finnish (NFE) AF: 0.338 AC: 22945 AN: 67960

Other (OTH) AF: 0.367 AC: 776 AN: 2112

Alfa AF: 0.356 Hom.: 11260

Bravo AF: 0.395

Asia WGS AF: 0.389 AC: 1355 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 09, 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	-0.83
CADD	Benign	4.0
DANN	Benign	0.28
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7077126; hg19: chr10-122668296; COSMIC: COSV54786543; COSMIC: COSV54786543;