chr2-86451218-A-G

Position:

• chr2-86451218-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000312912.10(KDM3A):​c.453+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: KDM3A ENST00000312912.10 splice_region, intron
• Scores: Splicing: ADA: 0.0004755
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

Genes affected

KDM3A (HGNC:20815): (lysine demethylase 3A) Enables androgen receptor binding activity; histone H3-methyl-lysine-9 demethylase activity; and iron ion binding activity. Involved in several processes, including androgen receptor signaling pathway; formaldehyde biosynthetic process; and histone H3-K9 demethylation. Located in nucleoplasm. Implicated in cervical cancer and colon cancer. Biomarker of Ewing sarcoma; hepatocellular carcinoma; nasopharynx carcinoma; and prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

KDM3A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-86451218-A-G is Benign according to our data. Variant chr2-86451218-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 669122.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3A	NM_018433.6	c.453+5A>G		splice_region_variant, intron_variant		ENST00000312912.10	NP_060903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM3A	ENST00000312912.10	c.453+5A>G		splice_region_variant, intron_variant		1	NM_018433.6	ENSP00000323659.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378216 Hom.: 0 Cov.: 22 AF XY: 0.00000145 AC XY: 1 AN XY: 689102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000275

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 12, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.030
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: rs1207228552; hg19: chr2-86678341;