16-649420-G-T

Variant names:

• chr16-649420-G-T
• rs758226655
• NM_145294.5:c.4G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145294.5(WDR90):​c.4G>T​(p.Ala2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,306,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• 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]

ENSG00000228201 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17311919).

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.4G>T	p.Ala2Ser	missense	Exon 1 of 41	NP_660337.3
	WDR90	NM_001438707.1		c.4G>T	p.Ala2Ser	missense	Exon 1 of 42	NP_001425636.1
	WDR90	NM_001438708.1		c.4G>T	p.Ala2Ser	missense	Exon 1 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.4G>T	p.Ala2Ser	missense	Exon 1 of 41	ENSP00000293879.4	Q96KV7-1
	WDR90	ENST00000420061.6	TSL:1	n.68G>T		non_coding_transcript_exon	Exon 1 of 17
	WDR90	ENST00000549648.5	TSL:1	n.68G>T		non_coding_transcript_exon	Exon 1 of 17

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 5234 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 12 AN: 1154620 Hom.: 0 Cov.: 29 AF XY: 0.00000901 AC XY: 5 AN XY: 555100

African (AFR) AF: 0.0000427 AC: 1 AN: 23396

American (AMR) AF: 0.00 AC: 0 AN: 8912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15714

East Asian (EAS) AF: 0.00 AC: 0 AN: 27130

South Asian (SAS) AF: 0.000274 AC: 11 AN: 40200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3360

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 962968

Other (OTH) AF: 0.00 AC: 0 AN: 46744

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152272 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ExAC AF: 0.0000125 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.98
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.033
Sift	Benign	0.030	D
Sift4G	Benign	0.23	T
Polyphen		0.43	B
Vest4		0.12
MutPred		0.34		Loss of catalytic residue at A2 (P = 0.0539)
MVP		0.25
MPC		0.35
ClinPred		0.29	T
GERP RS		0.83
PromoterAI		0.070	Neutral
Varity_R		0.14
gMVP		0.15
Mutation Taster		=95/5	polymorphism

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: rs758226655; hg19: chr16-699420;