rs11241095

Variant names:

• chr5-111103810-A-C
• rs11241095
• NM_139281.3:c.622A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-111103810-A-C
• chr5-111103810-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139281.3(WDR36):​c.622A>C​(p.Ile208Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I208V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 51 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16839859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.622A>C	p.Ile208Leu	missense_variant	Exon 7 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.622A>C	p.Ile208Leu	missense_variant	Exon 7 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.622A>C	p.Ile208Leu	missense_variant	Exon 7 of 23	1	NM_139281.3	ENSP00000424628.3
WDR36	ENST00000504122.2	n.504A>C		non_coding_transcript_exon_variant	Exon 5 of 5	4
WDR36	ENST00000505303.5	n.758A>C		non_coding_transcript_exon_variant	Exon 7 of 15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 22859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.4
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.
PhyloP100		0.27
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;.;.
REVEL	Benign	0.075
Sift4G	Benign	0.16	T;T;T
Polyphen		0.011	B;B;.
Vest4		0.27
MutPred		0.47		Loss of catalytic residue at L266 (P = 0.3899);Loss of catalytic residue at L266 (P = 0.3899);.;
MVP		0.44
MPC		0.030
ClinPred		0.68	D
GERP RS		0.61
Varity_R		0.52
gMVP		0.50
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11241095; hg19: chr5-110439509;