Variant 3-52278303-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025222.4(WDR82):c.59A>G(p.Asn20Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WDR82
NM_025222.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.10

Variant links:

Genes affected

WDR82 (HGNC:28826): (WD repeat domain 82) TMEM113 (WDR82) is a component of the mammalian SET1A (MIM 611052)/SET1B (MIM 611055) histone H3-Lys4 methyltransferase complexes (Lee and Skalnik, 2005 [PubMed 16253997]; Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Jul 2010]

WDR82 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR82	NM_025222.4 linkuse as main transcript	c.59A>G	p.Asn20Ser	missense_variant	1/9	ENST00000296490.8	NP_079498.2	Q6UXN9A0A024R333
WDR82	XM_011534136.3 linkuse as main transcript	c.-84A>G		5_prime_UTR_variant	1/8		XP_011532438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR82	ENST00000296490.8 linkuse as main transcript	c.59A>G	p.Asn20Ser	missense_variant	1/9	1	NM_025222.4	ENSP00000296490.3	Q6UXN9
WDR82	ENST00000469000.5 linkuse as main transcript	c.-345A>G		5_prime_UTR_variant	1/6	5		ENSP00000420779.2	C9JBU3
WDR82	ENST00000463624.1 linkuse as main transcript	c.-182+6225A>G		intron_variant		4		ENSP00000417313.2	C9J355

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243500

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

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:

6.86e-7

AC:

AN:

1457140

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 08, 2024

The c.59A>G (p.N20S) alteration is located in exon 1 (coding exon 1) of the WDR82 gene. This alteration results from a A to G substitution at nucleotide position 59, causing the asparagine (N) at amino acid position 20 to be replaced by a serine (S). 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

0.73

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.26

Sift

Benign

0.25

Sift4G

Benign

0.28

Polyphen

0.73

Vest4

0.48

MutPred

0.60

Gain of glycosylation at S21 (P = 0.0171);

MVP

0.31

MPC

1.8

ClinPred

0.98

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.52

gMVP

0.62

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