Genetic Variant WDR54:p.Ser68Gly (chr2-74422355-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032118.4(WDR54):c.202A>G(p.Ser68Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,798 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S68R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WDR54
NM_032118.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.60

Publications

0 publications found

Variant links:

Genes affected

WDR54 (HGNC:25770): (WD repeat domain 54) Enables protein homodimerization activity. Involved in negative regulation of receptor internalization; regulation of MAPK cascade; and regulation of epidermal growth factor receptor signaling pathway. Located in vesicle. [provided by Alliance of Genome Resources, Apr 2022]

WDR54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14613092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR54	NM_032118.4	MANE Select	c.202A>G	p.Ser68Gly	missense	Exon 2 of 10	NP_115494.1	Q9H977-1
WDR54	NM_001320823.2		c.247A>G	p.Ser83Gly	missense	Exon 2 of 10	NP_001307752.1	Q9H977-4
WDR54	NM_001320824.2		c.202A>G	p.Ser68Gly	missense	Exon 2 of 10	NP_001307753.1	Q9H977-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR54	ENST00000348227.4	TSL:1 MANE Select	c.202A>G	p.Ser68Gly	missense	Exon 2 of 10	ENSP00000006526.6	Q9H977-1
WDR54	ENST00000465134.5	TSL:1	n.612A>G		non_coding_transcript_exon	Exon 1 of 7
WDR54	ENST00000861017.1		c.202A>G	p.Ser68Gly	missense	Exon 2 of 10	ENSP00000531076.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111210

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

Eigen

Benign

-0.16

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.56

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

3.6

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

REVEL

Benign

0.088

Sift

Benign

0.12

Sift4G

Benign

0.16

Polyphen

0.0020

Vest4

0.36

MutPred

0.32

Loss of glycosylation at S68 (P = 0.0631)

MVP

0.26

MPC

0.20

ClinPred

0.74

GERP RS

5.5

Varity_R

0.12

gMVP

0.29

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over