5-111111042-C-A

Variant names:

• chr5-111111042-C-A
• rs13161853
• NM_139281.3:c.1607+89C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139281.3(WDR36):​c.1607+89C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,557,842 control chromosomes in the GnomAD database, including 175,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20145 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155266 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95
• Publications: 9 publications found

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) 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. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

WDR36 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, G

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-111111042-C-A is Benign according to our data. Variant chr5-111111042-C-A is described in ClinVar as Benign. ClinVar VariationId is 1263868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	NM_139281.3	MANE Select	c.1607+89C>A		intron	N/A	NP_644810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.1607+89C>A		intron	N/A	ENSP00000424628.3
	WDR36	ENST00000505303.5	TSL:5	n.1743+89C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.509 AC: 76975 AN: 151214 Hom.: 20119 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.463 AC: 650627 AN: 1406510 Hom.: 155266 Cov.: 24 AF XY: 0.469 AC XY: 329436 AN XY: 703026

African (AFR) AF: 0.601 AC: 19297 AN: 32132

American (AMR) AF: 0.618 AC: 27432 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 12436 AN: 25670

East Asian (EAS) AF: 0.357 AC: 14026 AN: 39332

South Asian (SAS) AF: 0.671 AC: 56894 AN: 84824

European-Finnish (FIN) AF: 0.517 AC: 27494 AN: 53220

Middle Eastern (MID) AF: 0.548 AC: 3092 AN: 5638

European-Non Finnish (NFE) AF: 0.435 AC: 462455 AN: 1062852

Other (OTH) AF: 0.470 AC: 27501 AN: 58458

GnomAD4 genome AF: 0.509 AC: 77054 AN: 151332 Hom.: 20145 Cov.: 32 AF XY: 0.516 AC XY: 38117 AN XY: 73916

African (AFR) AF: 0.602 AC: 24908 AN: 41366

American (AMR) AF: 0.528 AC: 7999 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1662 AN: 3446

East Asian (EAS) AF: 0.388 AC: 2002 AN: 5154

South Asian (SAS) AF: 0.673 AC: 3246 AN: 4826

European-Finnish (FIN) AF: 0.536 AC: 5643 AN: 10534

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30059 AN: 67548

Other (OTH) AF: 0.495 AC: 1040 AN: 2102

Alfa AF: 0.382 Hom.: 1190

Bravo AF: 0.505

Asia WGS AF: 0.524 AC: 1823 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.036
DANN	Benign	0.26
PhyloP100		-1.9
Mutation Taster		=12/88	disease causing (long InDel)

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: rs13161853; hg19: chr5-110446741; COSMIC: COSV106065708;