rs8191612

Variant names:

• chr8-11779766-C-G
• rs8191612
• NM_145043.4:c.307C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11779766-C-G
• chr8-11779766-C-T

Variant summary

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

The NM_145043.4(NEIL2):​c.307C>G​(p.Arg103Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEIL2 NM_145043.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

Genes affected

NEIL2 (HGNC:18956): (nei like DNA glycosylase 2) This gene encodes a member of the Fpg/Nei family of DNA glycosylases. These glycosylases initiate the first step in base excision repair by cleaving oxidatively damaged bases and introducing a DNA strand break via their abasic site lyase activity. This enzyme is primarily associated with DNA repair during transcription and acts prefentially on cytosine-derived lesions, particularly 5-hydroxyuracil and 5-hydroxycytosine. It contains an N-terminal catalytic domain, a hinge region, and a C-terminal DNA-binding domain with helix-two-turn-helix and zinc finger motifs. This enzyme interacts with the X-ray cross complementing factor 1 scaffold protein as part of a multi-protein DNA repair complex. A pseudogene of this gene has been identified. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0475716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.307C>G	p.Arg103Gly	missense_variant	Exon 3 of 5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.307C>G	p.Arg103Gly	missense_variant	Exon 3 of 5	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.8
DANN	Benign	0.89
DEOGEN2	Benign	0.0026	T;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.24	.;.;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N;N;.;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.13	N;N;N;N
REVEL	Benign	0.098
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.092
MutPred		0.32		Loss of methylation at R103 (P = 0.0158);Loss of methylation at R103 (P = 0.0158);.;Loss of methylation at R103 (P = 0.0158);
MVP		0.12
MPC		0.0036
ClinPred		0.062	T
GERP RS		-4.9
Varity_R		0.049
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs8191612; hg19: chr8-11637275;