2-28914120-A-G

Position:

• chr2-28914120-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015131.3(WDR43):​c.658A>G​(p.Arg220Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WDR43 NM_015131.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15869907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR43	NM_015131.3	c.658A>G	p.Arg220Gly	missense_variant	5/18	ENST00000407426.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR43	ENST00000407426.8	c.658A>G	p.Arg220Gly	missense_variant	5/18	1	NM_015131.3	P1
WDR43	ENST00000296126.6	c.115A>G	p.Arg39Gly	missense_variant	4/8	5
WDR43	ENST00000440983.1	c.391A>G	p.Arg131Gly	missense_variant	5/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Aug 09, 2021

The c.658A>G (p.R220G) alteration is located in exon 5 (coding exon 5) of the WDR43 gene. This alteration results from a A to G substitution at nucleotide position 658, causing the arginine (R) at amino acid position 220 to be replaced by a glycine (G). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.056	T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	2.0	M;.;.
MutationTaster	Benign	0.89	D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.038	D;T;T
Sift4G	Uncertain	0.017	D;T;D
Polyphen		0.75	P;.;.
Vest4		0.47
MutPred		0.44		Gain of sheet (P = 0.0149);.;.;
MVP		0.16
MPC		0.21
ClinPred		0.39	T
GERP RS		1.1
Varity_R		0.19
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr2-29136986;