5-111092532-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53

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]

ACMG classification

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/exons	MANE	UniProt
WDR36	NM_139281.3	c.76G>A	p.Asp26Asn	missense_variant	1/23	ENST00000513710.4
WDR36	XM_047416729.1	c.76G>A	p.Asp26Asn	missense_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR36	ENST00000513710.4	c.76G>A	p.Asp26Asn	missense_variant	1/23	1	NM_139281.3	P1
WDR36	ENST00000505303.5	n.212G>A		non_coding_transcript_exon_variant	1/15	5
WDR36	ENST00000515784.1	n.186G>A		non_coding_transcript_exon_variant	1/2	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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

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
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;.
MutationTaster	Benign	0.96	N;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;