Variant 5-37392067-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018034.4(WDR70):c.243G>T(p.Glu81Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000075 ( 0 hom. )

Consequence

WDR70
NM_018034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.734

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08655974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WDR70	NM_018034.4 linkuse as main transcript	c.243G>T	p.Glu81Asp	missense_variant	4/18	ENST00000265107.9
WDR70	NM_001345998.2 linkuse as main transcript	c.240G>T	p.Glu80Asp	missense_variant	4/18
WDR70	NM_001345999.2 linkuse as main transcript	c.177G>T	p.Glu59Asp	missense_variant	3/17
WDR70	XM_047417348.1 linkuse as main transcript	c.174G>T	p.Glu58Asp	missense_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDR70	ENST00000265107.9 linkuse as main transcript	c.243G>T	p.Glu81Asp	missense_variant	4/18	1	NM_018034.4	P1
WDR70	ENST00000504564.1 linkuse as main transcript	c.243G>T	p.Glu81Asp	missense_variant	4/12	1
WDR70	ENST00000511906.5 linkuse as main transcript	n.257G>T		non_coding_transcript_exon_variant	3/15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250010

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460672

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726596

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:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.243G>T (p.E81D) alteration is located in exon 4 (coding exon 4) of the WDR70 gene. This alteration results from a G to T substitution at nucleotide position 243, causing the glutamic acid (E) at amino acid position 81 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

0.0012

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.087

T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.71

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.28

Sift

Benign

0.40

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.12

B;D

Vest4

0.14

MutPred

0.11

Gain of MoRF binding (P = 0.1248);Gain of MoRF binding (P = 0.1248);

MVP

0.32

MPC

0.38

ClinPred

0.20

GERP RS

1.6

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.033

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over