5-111092532-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139281.3(WDR36):​c.76G>A​(p.Asp26Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

WDR36
NM_139281.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1436019).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR36NM_139281.3 linkc.76G>A p.Asp26Asn missense_variant Exon 1 of 23 ENST00000513710.4 NP_644810.2 Q8NI36
WDR36XM_047416729.1 linkc.76G>A p.Asp26Asn missense_variant Exon 1 of 21 XP_047272685.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR36ENST00000513710.4 linkc.76G>A p.Asp26Asn missense_variant Exon 1 of 23 1 NM_139281.3 ENSP00000424628.3 A0A0A0MTB8
WDR36ENST00000505303.5 linkn.212G>A non_coding_transcript_exon_variant Exon 1 of 15 5
WDR36ENST00000515784.1 linkn.186G>A non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.244G>A (p.D82N) alteration is located in exon 1 (coding exon 1) of the WDR36 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the aspartic acid (D) at amino acid position 82 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.062
T;T;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.20
N;N;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
1.2
N;.;.
REVEL
Benign
0.097
Sift4G
Benign
0.39
T;T;T
Polyphen
0.010
B;B;.
Vest4
0.30
MutPred
0.59
Gain of MoRF binding (P = 0.0417);Gain of MoRF binding (P = 0.0417);.;
MVP
0.27
MPC
0.028
ClinPred
1.0
D
GERP RS
4.1
Varity_R
0.28
gMVP
0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-110428230; API