Variant 5-37701121-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018034.4(WDR70):c.1256G>T(p.Gly419Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR70
NM_018034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35909796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR70	NM_018034.4 linkuse as main transcript	c.1256G>T	p.Gly419Val	missense_variant	12/18	ENST00000265107.9	NP_060504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR70	ENST00000265107.9 linkuse as main transcript	c.1256G>T	p.Gly419Val	missense_variant	12/18	1	NM_018034.4	ENSP00000265107	P1
WDR70	ENST00000510699.1 linkuse as main transcript	n.613G>T		non_coding_transcript_exon_variant	6/7	5
WDR70	ENST00000511906.5 linkuse as main transcript	n.1270G>T		non_coding_transcript_exon_variant	11/15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457100

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.1256G>T (p.G419V) alteration is located in exon 12 (coding exon 12) of the WDR70 gene. This alteration results from a G to T substitution at nucleotide position 1256, causing the glycine (G) at amino acid position 419 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.073

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

M_CAP

Benign

0.018

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0080

Polyphen

0.090

Vest4

0.60

MutPred

0.63

Loss of glycosylation at S418 (P = 0.0426);

MVP

0.19

MPC

0.66

ClinPred

0.88

GERP RS

2.1

Varity_R

0.19

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over