NM_139281.3:c.292-113G>A

Variant names:

• chr5-111098609-G-A
• rs13153937
• NM_139281.3:c.292-113G>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.292-113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 765,734 control chromosomes in the GnomAD database, including 43,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6832 hom., cov: 32)
  • Exomes 𝑓: 0.33 (36619 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84
• 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=-0.87).
• BP6: Variant 5-111098609-G-A is Benign according to our data. Variant chr5-111098609-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.292-113G>A		intron_variant	Intron 3 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.292-113G>A		intron_variant	Intron 3 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.292-113G>A		intron_variant	Intron 3 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000504122.2	n.174-113G>A		intron_variant	Intron 1 of 4	4
WDR36	ENST00000505303.5	n.428-113G>A		intron_variant	Intron 3 of 14	5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42548 AN: 151854 Hom.: 6823 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.334 AC: 205281 AN: 613762 Hom.: 36619 AF XY: 0.338 AC XY: 111277 AN XY: 329686

African (AFR) AF: 0.131 AC: 2168 AN: 16496

American (AMR) AF: 0.534 AC: 19288 AN: 36106

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 7055 AN: 19266

East Asian (EAS) AF: 0.311 AC: 10421 AN: 33460

South Asian (SAS) AF: 0.409 AC: 25799 AN: 63064

European-Finnish (FIN) AF: 0.392 AC: 17943 AN: 45762

Middle Eastern (MID) AF: 0.427 AC: 1128 AN: 2640

European-Non Finnish (NFE) AF: 0.305 AC: 111338 AN: 365388

Other (OTH) AF: 0.321 AC: 10141 AN: 31580

GnomAD4 genome AF: 0.280 AC: 42559 AN: 151972 Hom.: 6832 Cov.: 32 AF XY: 0.289 AC XY: 21439 AN XY: 74274

African (AFR) AF: 0.132 AC: 5466 AN: 41494

American (AMR) AF: 0.408 AC: 6228 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1708 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4818

European-Finnish (FIN) AF: 0.406 AC: 4286 AN: 10550

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20701 AN: 67920

Other (OTH) AF: 0.308 AC: 649 AN: 2104

Alfa AF: 0.297 Hom.: 1240

Bravo AF: 0.276

Asia WGS AF: 0.338 AC: 1176 AN: 3478

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.50
PhyloP100		-1.8
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: rs13153937; hg19: chr5-110434307; COSMIC: COSV72411257; COSMIC: COSV72411257;