2-202893193-A-G

Variant names:

• chr2-202893193-A-G
• rs7560547
• NM_018256.4:c.656-491T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018256.4(WDR12):​c.656-491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 152,090 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.089 (733 hom., cov: 32)
• Consequence: WDR12 NM_018256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 11 publications found

Genes affected

WDR12 (HGNC:14098): (WD repeat domain 12) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein is highly similar to the mouse WD repeat domain 12 protein at the amino acid level. The protein encoded by this gene is a component of a nucleolar protein complex that affects maturation of the large ribosomal subunit.[provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018256.4. 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
	WDR12	NM_018256.4	MANE Select	c.656-491T>C		intron	N/A	NP_060726.3
	WDR12	NM_001371664.1		c.242-491T>C		intron	N/A	NP_001358593.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR12	ENST00000261015.5	TSL:1 MANE Select	c.656-491T>C		intron	N/A	ENSP00000261015.4	Q9GZL7
	WDR12	ENST00000688520.1		c.656-491T>C		intron	N/A	ENSP00000509107.1	Q9GZL7
	WDR12	ENST00000923857.1		c.656-500T>C		intron	N/A	ENSP00000593916.1

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13496 AN: 151972 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0889 AC: 13518 AN: 152090 Hom.: 733 Cov.: 32 AF XY: 0.0860 AC XY: 6393 AN XY: 74350

African (AFR) AF: 0.0328 AC: 1361 AN: 41552

American (AMR) AF: 0.0957 AC: 1461 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.0148 AC: 77 AN: 5190

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1117 AN: 10546

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8475 AN: 67930

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.111 Hom.: 201

Bravo AF: 0.0876

Asia WGS AF: 0.0410 AC: 142 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.77
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

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: rs7560547; hg19: chr2-203757916;