rs770725122

Variant names:

• chr12-109088341-C-G
• ENST00000440112.2:c.452G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-109088341-C-G
• chr12-109088341-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001205179.2(ALKBH2):​c.452G>C​(p.Arg151Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALKBH2 NM_001205179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07511404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH2	NM_001145374.2	c.651G>C	p.Pro217Pro	synonymous_variant	Exon 4 of 4	ENST00000429722.3	NP_001138846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH2	ENST00000440112.2	c.452G>C	p.Arg151Pro	missense_variant	Exon 2 of 2	1		ENSP00000399820.2
ALKBH2	ENST00000429722.3	c.651G>C	p.Pro217Pro	synonymous_variant	Exon 4 of 4	5	NM_001145374.2	ENSP00000398181.1
ALKBH2	ENST00000343075.7	c.651G>C	p.Pro217Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000343021.3
ALKBH2	ENST00000619381.4	c.452G>C	p.Arg151Pro	missense_variant	Exon 3 of 3	5		ENSP00000478765.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	5.8
DANN	Uncertain	0.99
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.38	T;.
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	1.6	.;N
REVEL	Benign	0.050
Sift	Benign	0.033	.;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.18
MutPred		0.31		Loss of MoRF binding (P = 1e-04);Loss of MoRF binding (P = 1e-04);
MVP		0.49
ClinPred		0.18	T
GERP RS		2.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-109526146;