rs978949559

Variant names:

• chr2-189458803-C-G
• rs978949559
• NM_032168.3:c.620C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-189458803-C-G
• chr2-189458803-C-T

Variant summary

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

The NM_032168.3(WDR75):​c.620C>G​(p.Thr207Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T207I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR75 NM_032168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• Publications: 0 publications found

Genes affected

WDR75 (HGNC:25725): (WD repeat domain 75) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in nucleolus. [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_032168.3. 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
	WDR75	NM_032168.3	MANE Select	c.620C>G	p.Thr207Arg	missense	Exon 7 of 21	NP_115544.1	Q8IWA0
	WDR75	NM_001303096.2		c.428C>G	p.Thr143Arg	missense	Exon 8 of 22	NP_001290025.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR75	ENST00000314761.9	TSL:1 MANE Select	c.620C>G	p.Thr207Arg	missense	Exon 7 of 21	ENSP00000314193.4	Q8IWA0
	WDR75	ENST00000427960.5	TSL:1	n.*1984C>G		non_coding_transcript_exon	Exon 7 of 21	ENSP00000400728.1	F8WC81
	WDR75	ENST00000427960.5	TSL:1	n.*1984C>G		3_prime_UTR	Exon 7 of 21	ENSP00000400728.1	F8WC81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.56	N
PhyloP100		4.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.39
Sift	Benign	0.083	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.83
MutPred		0.52		Gain of MoRF binding (P = 0.0126)
MVP		0.25
MPC		0.72
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.92
Mutation Taster		=61/39	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: rs978949559; hg19: chr2-190323529;