Variant 9-134139896-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_017588.3(WDR5):c.19A>C(p.Lys7Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR5
NM_017588.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.95

Variant links:

Genes affected

WDR5 (HGNC:12757): (WD repeat domain 5) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 7 WD repeats. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

WDR5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity WDR5_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14446363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR5	NM_017588.3 linkuse as main transcript	c.19A>C	p.Lys7Gln	missense_variant	2/14	ENST00000358625.4	NP_060058.1	P61964

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR5	ENST00000358625.4 linkuse as main transcript	c.19A>C	p.Lys7Gln	missense_variant	2/14	1	NM_017588.3	ENSP00000351446.3	P61964
WDR5	ENST00000608739.5 linkuse as main transcript	c.19A>C	p.Lys7Gln	missense_variant	3/6	4		ENSP00000477449.1	V9GZ59
WDR5	ENST00000608937.5 linkuse as main transcript	c.19A>C	p.Lys7Gln	missense_variant	2/3	2		ENSP00000477000.1	V9GYQ5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250522

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135684

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461242

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726930

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000202

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Richard Lifton Laboratory, Yale University School of Medicine

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.84

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.28

.;.;N

REVEL

Benign

0.10

Sift

Benign

0.62

.;.;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.023

.;.;B

Vest4

0.86

MutPred

0.42

Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);

MVP

0.32

MPC

0.49

ClinPred

0.17

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.090

gMVP

0.50

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

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