chr6-169602260-G-C

Variant names:

• chr6-169602260-G-C
• rs773704528
• NM_182552.5:c.2383C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182552.5(WDR27):​c.2383C>G​(p.Pro795Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000511 in 1,565,726 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: WDR27 NM_182552.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR27	NM_182552.5	c.2383C>G	p.Pro795Ala	missense_variant	Exon 23 of 26	ENST00000448612.6	NP_872358.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR27	ENST00000448612.6	c.2383C>G	p.Pro795Ala	missense_variant	Exon 23 of 26	1	NM_182552.5	ENSP00000416289.1
ENSG00000285733	ENST00000648086.1	c.393C>G	p.Val131Val	synonymous_variant	Exon 4 of 8			ENSP00000497979.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152246 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000495 AC: 7 AN: 1413480 Hom.: 0 Cov.: 30 AF XY: 0.00000430 AC XY: 3 AN XY: 698270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000645

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.78	T
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Benign	0.21
Sift	Benign	0.056	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.087	.;B
Vest4		0.41
MutPred		0.59		Gain of methylation at R798 (P = 0.139);.;
MVP		0.18
MPC		0.078
ClinPred		0.89	D
GERP RS		3.7
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs773704528; hg19: chr6-170002356; COSMIC: COSV61205652;