rs1390264295

Variant names:

• chr6-169602278-A-T
• rs1390264295
• NM_182552.5:c.2365T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-169602278-A-T
• chr6-169602278-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182552.5(WDR27):​c.2365T>A​(p.Cys789Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 1,415,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: WDR27 NM_182552.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

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.2365T>A	p.Cys789Ser	missense	Exon 23 of 26	NP_872358.4
	WDR27	NM_001202550.2		c.1984T>A	p.Cys662Ser	missense	Exon 20 of 22	NP_001189479.1	A2RRH5-2
	WDR27	NM_001350623.2		c.1792T>A	p.Cys598Ser	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.2365T>A	p.Cys789Ser	missense	Exon 23 of 26	ENSP00000416289.1	A2RRH5-4
	WDR27	ENST00000423258.5	TSL:1	c.1984T>A	p.Cys662Ser	missense	Exon 20 of 22	ENSP00000397869.1	A2RRH5-2
	ENSG00000285733	ENST00000648086.1		c.375T>A	p.His125Gln	missense	Exon 4 of 8	ENSP00000497979.1	A0A3B3ITY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000353 AC: 5 AN: 1415134 Hom.: 0 Cov.: 30 AF XY: 0.00000429 AC XY: 3 AN XY: 699250

African (AFR) AF: 0.00 AC: 0 AN: 32434

American (AMR) AF: 0.00 AC: 0 AN: 38386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25304

East Asian (EAS) AF: 0.00 AC: 0 AN: 37328

South Asian (SAS) AF: 0.00 AC: 0 AN: 80026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1086814

Other (OTH) AF: 0.0000170 AC: 1 AN: 58672

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.97
Eigen	Benign	0.078
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0034	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.98	T
PhyloP100		3.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.55		Gain of disorder (P = 0.0046)
MVP		0.12
MPC		0.13
ClinPred		0.76	D
GERP RS		4.6
gMVP		0.37
Mutation Taster		=82/18	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: rs1390264295; hg19: chr6-170002374;