5-111124249-G-C

Variant names:

• chr5-111124249-G-C
• rs2290680
• NM_139281.3:c.2350+60G>C

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.2350+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 1,358,618 control chromosomes in the GnomAD database, including 6,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (644 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5999 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.310
• Publications: 5 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=-0.8).
• BP6: Variant 5-111124249-G-C is Benign according to our data. Variant chr5-111124249-G-C is described in ClinVar as Benign. ClinVar VariationId is 1250176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 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.2350+60G>C		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.2350+60G>C		intron	N/A	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13577 AN: 151906 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0864 AC: 104230 AN: 1206594 Hom.: 5999 AF XY: 0.0919 AC XY: 55851 AN XY: 607918

African (AFR) AF: 0.0867 AC: 2340 AN: 26994

American (AMR) AF: 0.0428 AC: 1710 AN: 39990

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 1660 AN: 24006

East Asian (EAS) AF: 0.0448 AC: 1590 AN: 35496

South Asian (SAS) AF: 0.230 AC: 17122 AN: 74392

European-Finnish (FIN) AF: 0.0930 AC: 4093 AN: 44032

Middle Eastern (MID) AF: 0.0755 AC: 323 AN: 4280

European-Non Finnish (NFE) AF: 0.0783 AC: 70999 AN: 906210

Other (OTH) AF: 0.0858 AC: 4393 AN: 51194

GnomAD4 genome AF: 0.0893 AC: 13583 AN: 152024 Hom.: 644 Cov.: 32 AF XY: 0.0921 AC XY: 6842 AN XY: 74288

African (AFR) AF: 0.0857 AC: 3553 AN: 41480

American (AMR) AF: 0.0608 AC: 928 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.0607 AC: 314 AN: 5170

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4818

European-Finnish (FIN) AF: 0.0983 AC: 1038 AN: 10556

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6158 AN: 67938

Other (OTH) AF: 0.0800 AC: 169 AN: 2112

Alfa AF: 0.0584 Hom.: 63

Bravo AF: 0.0797

Asia WGS AF: 0.145 AC: 501 AN: 3446

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 07, 2019

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	-0.80
CADD	Benign	5.5
DANN	Benign	0.74
PhyloP100		0.31
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: rs2290680; hg19: chr5-110459947; COSMIC: COSV72605392;