11-67231384-T-C

Variant names:

• chr11-67231384-T-C
• rs3927807
• NM_012308.3:c.1085-182T>C

Variant summary

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

The NM_012308.3(KDM2A):​c.1085-182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,046 control chromosomes in the GnomAD database, including 45,968 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 0.73 (45968 hom., cov: 30)
• Consequence: KDM2A NM_012308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

Genes affected

KDM2A (HGNC:13606): (lysine demethylase 2A) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM2A	NM_012308.3	c.1085-182T>C		intron_variant	Intron 11 of 20	ENST00000529006.7	NP_036440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM2A	ENST00000529006.7	c.1085-182T>C		intron_variant	Intron 11 of 20	1	NM_012308.3	ENSP00000432786.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110376 AN: 151928 Hom.: 45971 Cov.: 30

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.726 AC: 110389 AN: 152046 Hom.: 45968 Cov.: 30 AF XY: 0.729 AC XY: 54161 AN XY: 74326

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.778

Alfa AF: 0.886 Hom.: 26675

Bravo AF: 0.686

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.67

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: rs3927807; hg19: chr11-66998855;