10-1080466-C-G

Position:

• chr10-1080466-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_014023.4(WDR37):​c.386C>G​(p.Ser129Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR37 NM_014023.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.76

Genes affected

WDR37 (HGNC:31406): (WD repeat domain 37) 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. [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
• PP5: Variant 10-1080466-C-G is Pathogenic according to our data. Variant chr10-1080466-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 633616.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-1080466-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR37	NM_014023.4	c.386C>G	p.Ser129Cys	missense_variant	5/14	ENST00000263150.9	NP_054742.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR37	ENST00000263150.9	c.386C>G	p.Ser129Cys	missense_variant	5/14	1	NM_014023.4	ENSP00000263150	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neurooculocardiogenitourinary syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 23, 2024

- -

Congenital ocular coloboma;C0014544:Epilepsy;C0424605:Developmental delay;C1737329:Dysmorphism;C3714756:Intellectual disability;C5231391:Congenital cerebellar hypoplasia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health

May 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.;T;.;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D;D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Uncertain	2.1	M;.;.;.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.2	D;.;D;.;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.048	D;.;T;.;D;T
Sift4G	Benign	0.063	T;D;D;.;T;D
Polyphen		0.97	D;.;D;.;D;.
Vest4		0.61
MutPred		0.41		Loss of phosphorylation at S129 (P = 0.0327);Loss of phosphorylation at S129 (P = 0.0327);Loss of phosphorylation at S129 (P = 0.0327);Loss of phosphorylation at S129 (P = 0.0327);Loss of phosphorylation at S129 (P = 0.0327);.;
MVP		0.16
MPC		0.79
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1589088702; hg19: chr10-1126406;