chr11-62835718-C-T

Position:

• chr11-62835718-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369450.1(WDR74):​c.493G>A​(p.Glu165Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR74 NM_001369450.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.123283416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR74	NM_001369450.1	c.493G>A	p.Glu165Lys	missense_variant	5/11	ENST00000278856.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR74	ENST00000278856.9	c.493G>A	p.Glu165Lys	missense_variant	5/11	1	NM_001369450.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Dec 03, 2021

The c.493G>A (p.E165K) alteration is located in exon 6 (coding exon 5) of the WDR74 gene. This alteration results from a G to A substitution at nucleotide position 493, causing the glutamic acid (E) at amino acid position 165 to be replaced by a lysine (K). 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	0.081
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	.;T;T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D;.;.;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N;N;N;N;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.080	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.76	T;T;T;T;T
Sift4G	Benign	0.84	T;T;T;T;T
Polyphen		0.0070	B;B;B;B;B
Vest4		0.33
MutPred		0.39		Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);Gain of MoRF binding (P = 0.0145);.;
MVP		0.49
MPC		0.39
ClinPred		0.69	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62603190;