11-62834436-G-C

Position:

• chr11-62834436-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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]

WDR74 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR74	NM_001369450.1	c.710C>G	p.Pro237Arg	missense_variant	7/11	ENST00000278856.9	NP_001356379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR74	ENST00000278856.9	c.710C>G	p.Pro237Arg	missense_variant	7/11	1	NM_001369450.1	ENSP00000278856.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.710C>G (p.P237R) alteration is located in exon 8 (coding exon 7) of the WDR74 gene. This alteration results from a C to G substitution at nucleotide position 710, causing the proline (P) at amino acid position 237 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T;.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D
REVEL	Benign	0.19
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Uncertain	0.033	D;D;D;D;T
Polyphen		0.98	D;B;B;B;B
Vest4		0.79
MutPred		0.51		Gain of catalytic residue at P237 (P = 0.0217);Gain of catalytic residue at P237 (P = 0.0217);Gain of catalytic residue at P237 (P = 0.0217);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs767241559; hg19: chr11-62601908;