chr16-649420-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18146753).

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>C	p.Ala2Pro	missense	Exon 1 of 41	NP_660337.3
	WDR90	NM_001438707.1		c.4G>C	p.Ala2Pro	missense	Exon 1 of 42	NP_001425636.1
	WDR90	NM_001438708.1		c.4G>C	p.Ala2Pro	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>C	p.Ala2Pro	missense	Exon 1 of 41	ENSP00000293879.4	Q96KV7-1
	WDR90	ENST00000420061.6	TSL:1	n.68G>C		non_coding_transcript_exon	Exon 1 of 17
	WDR90	ENST00000549648.5	TSL:1	n.68G>C		non_coding_transcript_exon	Exon 1 of 17

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

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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 Cov.: 34

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	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
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.98
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.084
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.024	D
Polyphen		0.12	B
Vest4		0.29
MutPred		0.48		Loss of MoRF binding (P = 0.0402)
MVP		0.25
MPC		0.59
ClinPred		0.37	T
GERP RS		0.83
PromoterAI		-0.14	Neutral
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

Other links and lift over

dbSNP: rs758226655; hg19: chr16-699420;