2-28917896-G-C

Position:

• chr2-28917896-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015131.3(WDR43):​c.750G>C​(p.Gln250His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR43 NM_015131.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

Genes affected

WDR43 (HGNC:28945): (WD repeat domain 43) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR43	NM_015131.3	c.750G>C	p.Gln250His	missense_variant	6/18	ENST00000407426.8	NP_055946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR43	ENST00000407426.8	c.750G>C	p.Gln250His	missense_variant	6/18	1	NM_015131.3	ENSP00000384302.3
WDR43	ENST00000296126.6	c.207G>C	p.Gln69His	missense_variant	5/8	5		ENSP00000296126.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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 09, 2024

The c.750G>C (p.Q250H) alteration is located in exon 6 (coding exon 6) of the WDR43 gene. This alteration results from a G to C substitution at nucleotide position 750, causing the glutamine (Q) at amino acid position 250 to be replaced by a histidine (H). 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.073
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.079	T;T
Sift4G	Benign	0.17	T;D
Polyphen		0.36	B;.
Vest4		0.85
MutPred		0.63		Loss of sheet (P = 0.1501);.;
MVP		0.88
MPC		0.19
ClinPred		0.61	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.64

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: chr2-29140762;