chr2-202888349-T-C

Position:

• chr2-202888349-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.742-3814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,282 control chromosomes in the GnomAD database, including 742 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 (742 hom., cov: 32)
• Consequence: WDR12 NM_018256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

WDR12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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.742-3814A>G		intron_variant		ENST00000261015.5	NP_060726.3
WDR12	NM_001371664.1	c.328-3814A>G		intron_variant			NP_001358593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR12	ENST00000261015.5	c.742-3814A>G		intron_variant		1	NM_018256.4	ENSP00000261015.4
WDR12	ENST00000688520.1	c.742-3814A>G		intron_variant				ENSP00000509107.1
WDR12	ENST00000475611.1	n.272-3814A>G		intron_variant		3
WDR12	ENST00000477727.5	n.59-3814A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13524 AN: 152164 Hom.: 737 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0310

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: 0.0890 AC: 13546 AN: 152282 Hom.: 742 Cov.: 32 AF XY: 0.0860 AC XY: 6406 AN XY: 74462

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.0959

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.130

Alfa AF: 0.122 Hom.: 1556

Bravo AF: 0.0876

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	-0.94
CADD	Benign	0.25
DANN	Benign	0.70

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: rs7582720; hg19: chr2-203753072;