Genetic Variant NM_182552.5:c.2123G>T (chr6-169633047-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182552.5(WDR27):c.2123G>T(p.Arg708Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R708Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR27
NM_182552.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

Publications

3 publications found

Variant links:

Genes affected

WDR27 (HGNC:21248): (WD repeat domain 27) This gene encodes a protein with multiple WD repeats. Proteins with these repeats may form scaffolds for protein-protein interaction and play key roles in cell signalling. Alternative splicing results in multiple transcript variants, but the full-length structure of some of these variants cannot be determined. [provided by RefSeq, Nov 2015]

WDR27 links:

ENSG00000285733 (HGNC:):

ENSG00000285733 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182552.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR27	NM_182552.5	MANE Select	c.2123G>T	p.Arg708Leu	missense	Exon 21 of 26	NP_872358.4
WDR27	NM_001202550.2		c.1742G>T	p.Arg581Leu	missense	Exon 18 of 22	NP_001189479.1	A2RRH5-2
WDR27	NM_001350623.2		c.1550G>T	p.Arg517Leu	missense	Exon 16 of 21	NP_001337552.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR27	ENST00000448612.6	TSL:1 MANE Select	c.2123G>T	p.Arg708Leu	missense	Exon 21 of 26	ENSP00000416289.1	A2RRH5-4
WDR27	ENST00000423258.5	TSL:1	c.1742G>T	p.Arg581Leu	missense	Exon 18 of 22	ENSP00000397869.1	A2RRH5-2
ENSG00000285733	ENST00000648086.1		c.332-30726G>T		intron	N/A	ENSP00000497979.1	A0A3B3ITY5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707714

African (AFR)

AF:

0.00

AC:

AN:

33090

American (AMR)

AF:

0.00

AC:

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25894

East Asian (EAS)

AF:

0.00

AC:

AN:

38914

South Asian (SAS)

AF:

0.00

AC:

AN:

84158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090274

Other (OTH)

AF:

0.00

AC:

AN:

59046

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000427

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.047

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

PhyloP100

2.8

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.18

Sift

Benign

0.089

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.45

MutPred

0.59

Loss of methylation at R708 (P = 0.0944)

MVP

0.11

MPC

0.18

ClinPred

0.97

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.44

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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