16-649420-G-C

Position:

• chr16-649420-G-C

Variant summary

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

The NM_145294.5(WDR90):​c.4G>C​(p.Ala2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985

Genes affected

WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

WDR90 (HGNC:):

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=0.18146753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR90	NM_145294.5	c.4G>C	p.Ala2Pro	missense_variant	1/41	ENST00000293879.9	NP_660337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR90	ENST00000293879.9	c.4G>C	p.Ala2Pro	missense_variant	1/41	5	NM_145294.5	ENSP00000293879.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1154620 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 555100

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

Dec 21, 2022

The c.4G>C (p.A2P) alteration is located in exon 1 (coding exon 1) of the WDR90 gene. This alteration results from a G to C substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a proline (P). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0075	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.45	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	.;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.084
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.12	.;B
Vest4		0.29
MutPred		0.48		Loss of MoRF binding (P = 0.0402);Loss of MoRF binding (P = 0.0402);
MVP		0.25
MPC		0.59
ClinPred		0.37	T
GERP RS		0.83
Varity_R		0.21
gMVP		0.29

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: chr16-699420;