5-37479844-A-G

Position:

• chr5-37479844-A-G

Variant summary

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

The NM_018034.4(WDR70):​c.697A>G​(p.Lys233Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR70 NM_018034.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.76

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

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
WDR70	NM_018034.4	c.697A>G	p.Lys233Glu	missense_variant	8/18	ENST00000265107.9	NP_060504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR70	ENST00000265107.9	c.697A>G	p.Lys233Glu	missense_variant	8/18	1	NM_018034.4	ENSP00000265107.4
WDR70	ENST00000504564.1	c.697A>G	p.Lys233Glu	missense_variant	8/12	1		ENSP00000425841.1
WDR70	ENST00000510699.1	n.54A>G		non_coding_transcript_exon_variant	2/7	5
WDR70	ENST00000511906.5	n.711A>G		non_coding_transcript_exon_variant	7/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 30, 2024

The c.697A>G (p.K233E) alteration is located in exon 8 (coding exon 8) of the WDR70 gene. This alteration results from a A to G substitution at nucleotide position 697, causing the lysine (K) at amino acid position 233 to be replaced by a glutamic acid (E). 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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.65	P;P
Vest4		0.57
MutPred		0.51		Loss of ubiquitination at K233 (P = 0.0141);Loss of ubiquitination at K233 (P = 0.0141);
MVP		0.58
MPC		0.89
ClinPred		0.94	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-37479946;