chr5-37443295-C-G

Position:

• chr5-37443295-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018034.4(WDR70):​c.609C>G​(p.Asp203Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR70 NM_018034.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227

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]

WDR70 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR70	NM_018034.4	c.609C>G	p.Asp203Glu	missense_variant	7/18	ENST00000265107.9	NP_060504.1
WDR70	NM_001345998.2	c.606C>G	p.Asp202Glu	missense_variant	7/18		NP_001332927.1
WDR70	NM_001345999.2	c.543C>G	p.Asp181Glu	missense_variant	6/17		NP_001332928.1
WDR70	XM_047417348.1	c.540C>G	p.Asp180Glu	missense_variant	6/17		XP_047273304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR70	ENST00000265107.9	c.609C>G	p.Asp203Glu	missense_variant	7/18	1	NM_018034.4	ENSP00000265107.4
WDR70	ENST00000504564.1	c.609C>G	p.Asp203Glu	missense_variant	7/12	1		ENSP00000425841.1
WDR70	ENST00000511906.5	n.623C>G		non_coding_transcript_exon_variant	6/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 25, 2024

The c.609C>G (p.D203E) alteration is located in exon 7 (coding exon 7) of the WDR70 gene. This alteration results from a C to G substitution at nucleotide position 609, causing the aspartic acid (D) at amino acid position 203 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	0.96
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.51	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Pathogenic	4.3	H;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.030	D;T
Polyphen		1.0	D;D
Vest4		0.93
MutPred		0.87		Loss of ubiquitination at K207 (P = 0.0637);Loss of ubiquitination at K207 (P = 0.0637);
MVP		0.89
MPC		1.2
ClinPred		1.0	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.75

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: chr5-37443397;