rs6725887

Variant names:

• chr2-202881162-T-C
• rs6725887
• NM_018256.4:c.1195-225A>G

Variant summary

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

The NM_018256.4(WDR12):​c.1195-225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,252 control chromosomes in the GnomAD database, including 734 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 (734 hom., cov: 32)
• Consequence: WDR12 NM_018256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 161 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 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.1195-225A>G		intron	N/A	NP_060726.3
	WDR12	NM_001371664.1		c.781-225A>G		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.1195-225A>G		intron	N/A	ENSP00000261015.4	Q9GZL7
	WDR12	ENST00000688520.1		c.1195-225A>G		intron	N/A	ENSP00000509107.1	Q9GZL7
	WDR12	ENST00000923857.1		c.1186-225A>G		intron	N/A	ENSP00000593916.1

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13484 AN: 152134 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.0887 AC: 13506 AN: 152252 Hom.: 734 Cov.: 32 AF XY: 0.0858 AC XY: 6390 AN XY: 74452

African (AFR) AF: 0.0326 AC: 1354 AN: 41558

American (AMR) AF: 0.0958 AC: 1465 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5178

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4830

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10594

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

European-Non Finnish (NFE) AF: 0.125 AC: 8469 AN: 68012

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.111 Hom.: 2409

Bravo AF: 0.0874

Asia WGS AF: 0.0410 AC: 143 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.64
PhyloP100		0.094
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: rs6725887; hg19: chr2-203745885;