rs377120387

Variant names:

• chr6-169602313-C-T
• rs377120387
• NM_182552.5:c.2330G>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.2330G>A​(p.Arg777His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,545,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: WDR27 NM_182552.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86
• 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=0.24940985).

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.2330G>A	p.Arg777His	missense	Exon 23 of 26	NP_872358.4
	WDR27	NM_001202550.2		c.1949G>A	p.Arg650His	missense	Exon 20 of 22	NP_001189479.1	A2RRH5-2
	WDR27	NM_001350623.2		c.1757G>A	p.Arg586His	missense	Exon 18 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.2330G>A	p.Arg777His	missense	Exon 23 of 26	ENSP00000416289.1	A2RRH5-4
	WDR27	ENST00000423258.5	TSL:1	c.1949G>A	p.Arg650His	missense	Exon 20 of 22	ENSP00000397869.1	A2RRH5-2
	ENSG00000285733	ENST00000648086.1		c.340G>A	p.Ala114Thr	missense	Exon 4 of 8	ENSP00000497979.1	A0A3B3ITY5

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000530 AC: 9 AN: 169674 AF XY: 0.0000112

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000837

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000726

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000789 AC: 110 AN: 1393520 Hom.: 0 Cov.: 30 AF XY: 0.0000714 AC XY: 49 AN XY: 686242

African (AFR) AF: 0.0000313 AC: 1 AN: 31926

American (AMR) AF: 0.00 AC: 0 AN: 36662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 36332

South Asian (SAS) AF: 0.0000383 AC: 3 AN: 78364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.0000961 AC: 103 AN: 1072254

Other (OTH) AF: 0.0000521 AC: 3 AN: 57632

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.0000951 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Pathogenic	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T
PhyloP100		1.9
ClinPred		0.64	D
GERP RS		4.6
Mutation Taster		=84/16	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: rs377120387; hg19: chr6-170002409; COSMIC: COSV61206983;