Variant 14-100381547-C-G 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_001161476.3(WDR25):c.623C>G(p.Pro208Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,614,016 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

WDR25
NM_001161476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.542

Variant links:

Genes affected

WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

WDR25 links:

WDR25 (HGNC:):

WDR25 links:

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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=0.094812095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR25	NM_001161476.3 linkuse as main transcript	c.623C>G	p.Pro208Arg	missense_variant	2/7	ENST00000402312.8	NP_001154948.1	Q64LD2-1A0A384NPW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR25	ENST00000402312.8 linkuse as main transcript	c.623C>G	p.Pro208Arg	missense_variant	2/7	2	NM_001161476.3	ENSP00000385540.3		Q64LD2-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251194

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000238

AC:

348

AN:

1461764

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000151

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

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

Sep 26, 2022

The c.623C>G (p.P208R) alteration is located in exon 2 (coding exon 1) of the WDR25 gene. This alteration results from a C to G substitution at nucleotide position 623, causing the proline (P) at amino acid position 208 to be replaced by an arginine (R). 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

0.086

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T;T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.76

.;.;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.099

T;T;T;D

Sift4G

Uncertain

0.055

T;T;T;D

Polyphen

0.95

P;P;P;.

Vest4

0.30

MVP

0.18

MPC

0.33

ClinPred

0.25

GERP RS

4.8

Varity_R

0.15

gMVP

0.17

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