chr11-67231777-C-A

Variant names:

• chr11-67231777-C-A
• rs1305987006
• NM_012308.3:c.1296C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_012308.3(KDM2A):​c.1296C>A​(p.Gly432Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KDM2A NM_012308.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.519
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-67231777-C-A is Benign according to our data. Variant chr11-67231777-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.519 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012308.3. 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
	KDM2A	NM_012308.3	MANE Select	c.1296C>A	p.Gly432Gly	synonymous	Exon 12 of 21	NP_036440.1	Q9Y2K7-1
	KDM2A	NR_027473.2		n.2166C>A		non_coding_transcript_exon	Exon 12 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM2A	ENST00000529006.7	TSL:1 MANE Select	c.1296C>A	p.Gly432Gly	synonymous	Exon 12 of 21	ENSP00000432786.1	Q9Y2K7-1
	KDM2A	ENST00000308783.9	TSL:1	c.1245C>A	p.Gly415Gly	synonymous	Exon 12 of 21	ENSP00000309302.6	I3VM54
	KDM2A	ENST00000398645.6	TSL:1	c.1296C>A	p.Gly432Gly	synonymous	Exon 12 of 21	ENSP00000381640.2	Q9Y2K7-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1305987006; hg19: chr11-66999248;