NM_001145374.2:c.106A>C

Variant names:

• chr12-109092681-T-G
• NM_001145374.2:c.106A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145374.2(ALKBH2):​c.106A>C​(p.Ser36Arg) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALKBH2 NM_001145374.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.209
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043547034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145374.2. 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
	ALKBH2	NM_001145374.2	MANE Select	c.106A>C	p.Ser36Arg	missense	Exon 2 of 4	NP_001138846.1	Q6NS38-1
	ALKBH2	NM_001001655.3		c.106A>C	p.Ser36Arg	missense	Exon 2 of 4	NP_001001655.1	Q6NS38-1
	ALKBH2	NM_001145375.2		c.106A>C	p.Ser36Arg	missense	Exon 2 of 4	NP_001138847.1	Q6NS38-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH2	ENST00000429722.3	TSL:5 MANE Select	c.106A>C	p.Ser36Arg	missense	Exon 2 of 4	ENSP00000398181.1	Q6NS38-1
	ALKBH2	ENST00000343075.7	TSL:1	c.106A>C	p.Ser36Arg	missense	Exon 2 of 4	ENSP00000343021.3	Q6NS38-1
	ALKBH2	ENST00000440112.2	TSL:1	c.106A>C	p.Ser36Arg	missense	Exon 1 of 2	ENSP00000399820.2	Q6NS38-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.8
DANN	Benign	0.94
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.21
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.034
Sift	Benign	0.20	T
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.17
MutPred		0.17		Loss of phosphorylation at S36 (P = 0.0098)
MVP		0.12
MPC		0.15
ClinPred		0.066	T
GERP RS		-1.5
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.28
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr12-109530486;