rs6722332

Positions:

• chr2-202880604-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018256.4(WDR12):​c.*256A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 223,008 control chromosomes in the GnomAD database, including 1,223 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 (739 hom., cov: 32)
  • Exomes 𝑓: 0.099 (484 hom.)
• Consequence: WDR12 NM_018256.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR12	NM_018256.4	c.*256A>G		3_prime_UTR_variant	13/13	ENST00000261015.5	NP_060726.3
WDR12	NM_001371664.1	c.*256A>G		3_prime_UTR_variant	12/12		NP_001358593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR12	ENST00000261015.5	c.*256A>G		3_prime_UTR_variant	13/13	1	NM_018256.4	ENSP00000261015	P1
WDR12	ENST00000688520.1	c.*256A>G		3_prime_UTR_variant	13/13			ENSP00000509107	P1
WDR12	ENST00000467777.1	n.479A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13440 AN: 151572 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.0992 AC: 7074 AN: 71322 Hom.: 484 Cov.: 2 AF XY: 0.0982 AC XY: 3652 AN XY: 37188

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0865

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.00908

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0887 AC: 13461 AN: 151686 Hom.: 739 Cov.: 32 AF XY: 0.0859 AC XY: 6365 AN XY: 74128

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.0955

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.130

Alfa AF: 0.111 Hom.: 270

Bravo AF: 0.0874

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.75

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: rs6722332; hg19: chr2-203745327;