3-122414732-C-T

Variant names:

• chr3-122414732-C-T
• NM_019069.4:c.797G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019069.4(WDR5B):​c.797G>A​(p.Gly266Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G266S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR5B NM_019069.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 0 publications found

Genes affected

WDR5B (HGNC:17826): (WD repeat domain 5B) This intronless gene encodes a protein containing several WD40 repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, including a trp-asp at the C-terminal end. The encoded protein may mediate protein-protein interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019069.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR5B	NM_019069.4	MANE Select	c.797G>A	p.Gly266Asp	missense	Exon 1 of 1	NP_061942.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR5B	ENST00000330689.6	TSL:6 MANE Select	c.797G>A	p.Gly266Asp	missense	Exon 1 of 1	ENSP00000330381.4	Q86VZ2
	WDR5B	ENST00000920957.1		c.797G>A	p.Gly266Asp	missense	Exon 2 of 2	ENSP00000591016.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-1.1	N
PhyloP100		2.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.29
Sift	Benign	0.16	T
Sift4G	Benign	0.12	T
Polyphen		0.0020	B
Vest4		0.63
MutPred		0.68		Loss of methylation at K268 (P = 0.0803)
MVP		0.76
MPC		0.097
ClinPred		0.63	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.53
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr3-122133579;