5-111119021-A-T

Variant names:

• chr5-111119021-A-T
• NM_139281.3:c.1805A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_139281.3(WDR36):​c.1805A>T​(p.Asp602Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D602G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR36 NM_139281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.04

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR36	NM_139281.3	c.1805A>T	p.Asp602Val	missense_variant	Exon 17 of 23	ENST00000513710.4	NP_644810.2
WDR36	XM_047416729.1	c.1805A>T	p.Asp602Val	missense_variant	Exon 17 of 21		XP_047272685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR36	ENST00000513710.4	c.1805A>T	p.Asp602Val	missense_variant	Exon 17 of 23	1	NM_139281.3	ENSP00000424628.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;D;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	4.0	H;H;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-8.3	D;.;.
REVEL	Pathogenic	0.92
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.88
MutPred		0.71		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);.;
MVP		0.95
MPC		0.26
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.81
gMVP		0.76

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: chr5-110454719;