chr5-111099792-C-G

Variant names:

• chr5-111099792-C-G
• rs2416257
• NM_139281.3:c.410-797C>G

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.410-797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,778 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 30 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.410-797C>G		intron_variant	Intron 4 of 22	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.410-797C>G		intron_variant	Intron 4 of 20		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.410-797C>G		intron_variant	Intron 4 of 22	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000504122.2	n.292-797C>G		intron_variant	Intron 2 of 4	4
WDR36	ENST00000505303.5	n.546-797C>G		intron_variant	Intron 4 of 14	5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151778 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151778 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74122

African (AFR) AF: 0.0000242 AC: 1 AN: 41320

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 6602

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.071
DANN	Benign	0.43
PhyloP100		-2.2

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: rs2416257; hg19: chr5-110435490;