chr5-111107529-C-A

Variant names:

• chr5-111107529-C-A
• rs10043631
• NM_139281.3:c.1326+90C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139281.3(WDR36):​c.1326+90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.1326+90C>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.1326+90C>A		intron	N/A	ENSP00000424628.3
	WDR36	ENST00000505303.5	TSL:5	n.1462+90C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369784 Hom.: 0 AF XY: 0.00000147 AC XY: 1 AN XY: 680976

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30822

American (AMR) AF: 0.00 AC: 0 AN: 37510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24682

East Asian (EAS) AF: 0.00 AC: 0 AN: 37966

South Asian (SAS) AF: 0.00 AC: 0 AN: 78668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4238

European-Non Finnish (NFE) AF: 9.49e-7 AC: 1 AN: 1053386

Other (OTH) AF: 0.00 AC: 0 AN: 56796

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.17
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10043631; hg19: chr5-110443228;