16-650090-A-G

Variant names:

• chr16-650090-A-G
• rs912656781
• NM_145294.5:c.202A>G

Variant summary

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

The NM_145294.5(WDR90):​c.202A>G​(p.Thr68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

Genes affected

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

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_145294.5. 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
	WDR90	NM_145294.5	MANE Select	c.202A>G	p.Thr68Ala	missense	Exon 3 of 41	NP_660337.3
	WDR90	NM_001438707.1		c.202A>G	p.Thr68Ala	missense	Exon 3 of 42	NP_001425636.1
	WDR90	NM_001438708.1		c.202A>G	p.Thr68Ala	missense	Exon 3 of 42	NP_001425637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR90	ENST00000293879.9	TSL:5 MANE Select	c.202A>G	p.Thr68Ala	missense	Exon 3 of 41	ENSP00000293879.4	Q96KV7-1
	WDR90	ENST00000420061.6	TSL:1	n.266A>G		non_coding_transcript_exon	Exon 3 of 17
	WDR90	ENST00000549648.5	TSL:1	n.266A>G		non_coding_transcript_exon	Exon 3 of 17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460710 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726666

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52338

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60372

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	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.71		Gain of helix (P = 0.0143)
MVP		0.30
MPC		0.55
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.32

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

Other links and lift over

dbSNP: rs912656781; hg19: chr16-700090;