11-62834436-G-C

Variant names:

• chr11-62834436-G-C
• rs767241559
• NM_001369450.1:c.710C>G

Variant summary

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

The NM_001369450.1(WDR74):​c.710C>G​(p.Pro237Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P237L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 26)
• Consequence: WDR74 NM_001369450.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

WDR74 (HGNC:25529): (WD repeat domain 74) Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nucleoplasm. Colocalizes with nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

STX5-DT (HGNC:55488): (STX5 divergent transcript)

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_001369450.1. 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
	WDR74	NM_001369450.1	MANE Select	c.710C>G	p.Pro237Arg	missense	Exon 7 of 11	NP_001356379.1	Q6RFH5-1
	WDR74	NM_001369447.1		c.752C>G	p.Pro251Arg	missense	Exon 7 of 11	NP_001356376.1
	WDR74	NM_001369451.1		c.710C>G	p.Pro237Arg	missense	Exon 8 of 12	NP_001356380.1	Q6RFH5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR74	ENST00000278856.9	TSL:1 MANE Select	c.710C>G	p.Pro237Arg	missense	Exon 7 of 11	ENSP00000278856.4	Q6RFH5-1
	WDR74	ENST00000311713.11	TSL:1	c.710C>G	p.Pro237Arg	missense	Exon 7 of 10	ENSP00000308931.7	Q6RFH5-2
	WDR74	ENST00000892916.1		c.752C>G	p.Pro251Arg	missense	Exon 8 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.19
Sift	Benign	0.10	T
Sift4G	Uncertain	0.033	D
Polyphen		0.98	D
Vest4		0.79
MutPred		0.51		Gain of catalytic residue at P237 (P = 0.0217)
MVP		0.60
MPC		0.43
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.66
Mutation Taster		=78/22	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: rs767241559; hg19: chr11-62601908;