Variant chr2-202907936-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018256.4(WDR12):c.65T>G(p.Phe22Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WDR12
NM_018256.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.48

Variant links:

Genes affected

WDR12 (HGNC:14098): (WD repeat domain 12) 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 is highly similar to the mouse WD repeat domain 12 protein at the amino acid level. The protein encoded by this gene is a component of a nucleolar protein complex that affects maturation of the large ribosomal subunit.[provided by RefSeq, Dec 2008]

WDR12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR12	NM_018256.4 linkuse as main transcript	c.65T>G	p.Phe22Cys	missense_variant	2/13	ENST00000261015.5	NP_060726.3
WDR12	NM_001371664.1 linkuse as main transcript	c.-234T>G		5_prime_UTR_variant	2/12		NP_001358593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR12	ENST00000261015.5 linkuse as main transcript	c.65T>G	p.Phe22Cys	missense_variant	2/13	1	NM_018256.4	ENSP00000261015	P1
WDR12	ENST00000688520.1 linkuse as main transcript	c.65T>G	p.Phe22Cys	missense_variant	2/13			ENSP00000509107	P1
WDR12	ENST00000477723.1 linkuse as main transcript	n.459T>G		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251424

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Apr 01, 2024

The c.65T>G (p.F22C) alteration is located in exon 2 (coding exon 2) of the WDR12 gene. This alteration results from a T to G substitution at nucleotide position 65, causing the phenylalanine (F) at amino acid position 22 to be replaced by a cysteine (C). 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

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.88

MutPred

0.55

Gain of catalytic residue at P21 (P = 0.0122);

MVP

0.48

MPC

0.56

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.73

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