12-109096844-T-C

Variant names:

• chr12-109096844-T-C
• rs2337395
• ENST00000861370.1:c.-152+1453A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000861370.1(ALKBH2):​c.-152+1453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,744 control chromosomes in the GnomAD database, including 24,217 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 0.55 (24217 hom., cov: 30)
• Consequence: ALKBH2 ENST00000861370.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 6 publications found

Genes affected

ALKBH2 (HGNC:32487): (alkB homolog 2, alpha-ketoglutarate dependent dioxygenase) The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the specific DNA lesions generated in single-stranded DNA. ALKBH2 and ALKBH3 (MIM 610603) are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine (Duncan et al., 2002 [PubMed 12486230]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000861370.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH2	ENST00000861370.1		c.-152+1453A>G		intron	N/A	ENSP00000531429.1
	ALKBH2	ENST00000861371.1		c.-2+1453A>G		intron	N/A	ENSP00000531430.1
	ALKBH2	ENST00000861372.1		c.-2+763A>G		intron	N/A	ENSP00000531431.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83344 AN: 151626 Hom.: 24168 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.550 AC: 83451 AN: 151744 Hom.: 24217 Cov.: 30 AF XY: 0.553 AC XY: 40991 AN XY: 74178

African (AFR) AF: 0.725 AC: 30025 AN: 41392

American (AMR) AF: 0.609 AC: 9288 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3466

East Asian (EAS) AF: 0.722 AC: 3696 AN: 5118

South Asian (SAS) AF: 0.508 AC: 2446 AN: 4812

European-Finnish (FIN) AF: 0.498 AC: 5238 AN: 10528

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29605 AN: 67878

Other (OTH) AF: 0.538 AC: 1130 AN: 2100

Alfa AF: 0.503 Hom.: 2543

Bravo AF: 0.564

Asia WGS AF: 0.630 AC: 2190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2337395;

hg19: chr12-109534649;