Genetic Variant NM_032118.4:c.202A>T (chr2-74422355-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032118.4(WDR54):c.202A>T(p.Ser68Cys) 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. 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40361255).

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>T	p.Ser68Cys	missense	Exon 2 of 10	NP_115494.1	Q9H977-1
WDR54	NM_001320823.2		c.247A>T	p.Ser83Cys	missense	Exon 2 of 10	NP_001307752.1	Q9H977-4
WDR54	NM_001320824.2		c.202A>T	p.Ser68Cys	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>T	p.Ser68Cys	missense	Exon 2 of 10	ENSP00000006526.6	Q9H977-1
WDR54	ENST00000465134.5	TSL:1	n.612A>T		non_coding_transcript_exon	Exon 1 of 7
WDR54	ENST00000861017.1		c.202A>T	p.Ser68Cys	missense	Exon 2 of 10	ENSP00000531076.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460798

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.0000299

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:

0.00

AC:

AN:

1111210

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.68

M_CAP

Benign

0.037

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

PhyloP100

3.6

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.60

MutPred

0.48

Loss of disorder (P = 0.0138)

MVP

0.34

MPC

0.43

ClinPred

0.97

GERP RS

5.5

Varity_R

0.14

gMVP

0.39

Mutation Taster

=77/23

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over