chr6-169572543-C-CAAAAAAAAAAAAAAA

Variant names:

• chr6-169572543-C-CAAAAAAAAAAAAAAA
• rs376783967
• NM_182552.5:c.2524-18_2524-4dupTTTTTTTTTTTTTTT

Variant summary

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

The NM_182552.5(WDR27):​c.2524-18_2524-4dupTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000011 (0 hom., cov: 0)
• Consequence: WDR27 NM_182552.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• 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 0 ACMG points.

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.2524-18_2524-4dupTTTTTTTTTTTTTTT		splice_region intron	N/A	NP_872358.4
	WDR27	NM_001202550.2		c.2142+10278_2142+10292dupTTTTTTTTTTTTTTT		intron	N/A	NP_001189479.1	A2RRH5-2
	WDR27	NM_001350623.2		c.1950+10278_1950+10292dupTTTTTTTTTTTTTTT		intron	N/A	NP_001337552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR27	ENST00000448612.6	TSL:1 MANE Select	c.2524-4_2524-3insTTTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000416289.1	A2RRH5-4
	WDR27	ENST00000423258.5	TSL:1	c.2142+10292_2142+10293insTTTTTTTTTTTTTTT		intron	N/A	ENSP00000397869.1	A2RRH5-2
	ENSG00000285733	ENST00000648086.1		c.533+10292_533+10293insTTTTTTTTTTTTTTT		intron	N/A	ENSP00000497979.1	A0A3B3ITY5

Frequencies

GnomAD3 genomes AF: 0.0000108 AC: 1 AN: 92414 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000578

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000108 AC: 1 AN: 92396 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42762

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000578 AC: 1 AN: 17314

American (AMR) AF: 0.00 AC: 0 AN: 8040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2780

East Asian (EAS) AF: 0.00 AC: 0 AN: 2168

South Asian (SAS) AF: 0.00 AC: 0 AN: 2590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52916

Other (OTH) AF: 0.00 AC: 0 AN: 1276

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376783967; hg19: chr6-169972639;