Variant 14-100381627-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001161476.3(WDR25):c.703C>A(p.Pro235Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,455,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000096 ( 0 hom. )

Consequence

WDR25
NM_001161476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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:

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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=0.27791524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR25	NM_001161476.3 linkuse as main transcript	c.703C>A	p.Pro235Thr	missense_variant	2/7	ENST00000402312.8	NP_001154948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR25	ENST00000402312.8 linkuse as main transcript	c.703C>A	p.Pro235Thr	missense_variant	2/7	2	NM_001161476.3	ENSP00000385540	P1	Q64LD2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1455706

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724364

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:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000113

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

Jun 28, 2022

The c.703C>A (p.P235T) alteration is located in exon 2 (coding exon 1) of the WDR25 gene. This alteration results from a C to A substitution at nucleotide position 703, causing the proline (P) at amino acid position 235 to be replaced by a threonine (T). 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

0.23

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

.;.;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;.

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.2

D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.93

P;P;P;.

Vest4

0.38

MutPred

0.45

Gain of MoRF binding (P = 0.0517);Gain of MoRF binding (P = 0.0517);Gain of MoRF binding (P = 0.0517);Gain of MoRF binding (P = 0.0517);

MVP

0.055

MPC

0.18

ClinPred

0.95

GERP RS

3.6

Varity_R

0.16

gMVP

0.40

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