6-169632975-C-T

Variant names:

• chr6-169632975-C-T
• rs376239890
• NM_182552.5:c.2195G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182552.5(WDR27):​c.2195G>A​(p.Arg732Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000091 in 1,593,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R732W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: WDR27 NM_182552.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 1 publications found

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]

ENSG00000285733 (HGNC:):

ACMG classification

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=0.17562073).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	NM_182552.5	MANE Select	c.2195G>A	p.Arg732Gln	missense	Exon 21 of 26	NP_872358.4
	WDR27	NM_001202550.2		c.1814G>A	p.Arg605Gln	missense	Exon 18 of 22	NP_001189479.1	A2RRH5-2
	WDR27	NM_001350623.2		c.1622G>A	p.Arg541Gln	missense	Exon 16 of 21	NP_001337552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	ENST00000448612.6	TSL:1 MANE Select	c.2195G>A	p.Arg732Gln	missense	Exon 21 of 26	ENSP00000416289.1	A2RRH5-4
	WDR27	ENST00000423258.5	TSL:1	c.1814G>A	p.Arg605Gln	missense	Exon 18 of 22	ENSP00000397869.1	A2RRH5-2
	ENSG00000285733	ENST00000648086.1		c.332-30654G>A		intron	N/A	ENSP00000497979.1	A0A3B3ITY5

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000125 AC: 31 AN: 248508 AF XY: 0.000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000888 AC: 128 AN: 1441582 Hom.: 0 Cov.: 30 AF XY: 0.0000828 AC XY: 59 AN XY: 712546

African (AFR) AF: 0.0000301 AC: 1 AN: 33192

American (AMR) AF: 0.0000675 AC: 3 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39050

South Asian (SAS) AF: 0.00 AC: 0 AN: 85016

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53220

Middle Eastern (MID) AF: 0.000379 AC: 2 AN: 5280

European-Non Finnish (NFE) AF: 0.0000766 AC: 84 AN: 1096066

Other (OTH) AF: 0.000118 AC: 7 AN: 59356

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000363 AC: 3

ExAC AF: 0.000141 AC: 17

EpiCase AF: 0.000274

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Pathogenic	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.78	T
PhyloP100		3.8
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.39
MPC		0.17
ClinPred		0.95	D
GERP RS		5.0
gMVP		0.47
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs376239890; hg19: chr6-170033071;