chr2-28912618-A-G

Position:

• chr2-28912618-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015131.3(WDR43):​c.514A>G​(p.Ser172Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: WDR43 NM_015131.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR43	NM_015131.3	c.514A>G	p.Ser172Gly	missense_variant	4/18	ENST00000407426.8	NP_055946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR43	ENST00000407426.8	c.514A>G	p.Ser172Gly	missense_variant	4/18	1	NM_015131.3	ENSP00000384302.3
WDR43	ENST00000440983.1	c.247A>G	p.Ser83Gly	missense_variant	4/5	4		ENSP00000415355.1
WDR43	ENST00000296126	c.-30A>G		5_prime_UTR_variant	3/8	5		ENSP00000296126.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461648 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727106

Gnomad4 AFR exome AF: 0.0000597

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 06, 2024

The c.514A>G (p.S172G) alteration is located in exon 4 (coding exon 4) of the WDR43 gene. This alteration results from a A to G substitution at nucleotide position 514, causing the serine (S) at amino acid position 172 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	0.11
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.15
Sift	Benign	0.056	T;T
Sift4G	Uncertain	0.018	D;T
Polyphen		0.56	P;.
Vest4		0.44
MutPred		0.62		Loss of disorder (P = 0.0914);.;
MVP		0.29
MPC		0.25
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.17
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs367919374; hg19: chr2-29135484;