chr9-134140796-T-C

Position:

• chr9-134140796-T-C

Variant summary

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

The NM_017588.3(WDR5):​c.175T>C​(p.Trp59Arg) 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: 32)
• Consequence: WDR5 NM_017588.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.36

Genes affected

WDR5 (HGNC:12757): (WD repeat domain 5) 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. This protein contains 7 WD repeats. Alternatively spliced transcript variants encoding the same protein have been identified. [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 9-134140796-T-C is Pathogenic according to our data. Variant chr9-134140796-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3375461.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR5	NM_017588.3	c.175T>C	p.Trp59Arg	missense_variant	3/14	ENST00000358625.4	NP_060058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR5	ENST00000358625.4	c.175T>C	p.Trp59Arg	missense_variant	3/14	1	NM_017588.3	ENSP00000351446.3
WDR5	ENST00000608739.5	c.175T>C	p.Trp59Arg	missense_variant	4/6	4		ENSP00000477449.1
WDR5	ENST00000608937.5	c.*6T>C		downstream_gene_variant		2		ENSP00000477000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

WDR5-related neurodevelopmental delay Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn

Oct 07, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.46	.;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.3	.;D
REVEL	Uncertain	0.48
Sift	Benign	0.043	.;D
Sift4G	Uncertain	0.026	D;T
Polyphen		0.80	.;P
Vest4		0.89
MutPred		0.54		Gain of disorder (P = 0.01);Gain of disorder (P = 0.01);
MVP		0.61
MPC		1.0
ClinPred		0.96	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.72

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: chr9-137005918;