rs8191613

Variant names:

• chr8-11779767-G-A
• rs8191613
• NM_145043.4:c.308G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-11779767-G-A
• chr8-11779767-G-C
• chr8-11779767-G-T

Variant summary

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

The NM_145043.4(NEIL2):​c.308G>A​(p.Arg103Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,614,178 control chromosomes in the GnomAD database, including 2,267 homozygotes. 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. R103W) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.038 (265 hom., cov: 32)
  • Exomes 𝑓: 0.025 (2002 hom.)
• Consequence: NEIL2 NM_145043.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 25 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043165684).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.308G>A	p.Arg103Gln	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.308G>A	p.Arg103Gln	missense_variant	Exon 3 of 5	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5834 AN: 152182 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0450 AC: 11202 AN: 249024 AF XY: 0.0408

Gnomad AFR exome AF: 0.0511

Gnomad AMR exome AF: 0.0508

Gnomad ASJ exome AF: 0.00864

Gnomad EAS exome AF: 0.250

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.0338

GnomAD4 exome AF: 0.0252 AC: 36783 AN: 1461878 Hom.: 2002 Cov.: 32 AF XY: 0.0242 AC XY: 17614 AN XY: 727236

African (AFR) AF: 0.0574 AC: 1923 AN: 33480

American (AMR) AF: 0.0494 AC: 2209 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 269 AN: 26136

East Asian (EAS) AF: 0.275 AC: 10930 AN: 39700

South Asian (SAS) AF: 0.00729 AC: 629 AN: 86258

European-Finnish (FIN) AF: 0.0754 AC: 4026 AN: 53408

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.0135 AC: 15017 AN: 1112010

Other (OTH) AF: 0.0286 AC: 1725 AN: 60396

GnomAD4 genome AF: 0.0383 AC: 5838 AN: 152300 Hom.: 265 Cov.: 32 AF XY: 0.0420 AC XY: 3126 AN XY: 74476

African (AFR) AF: 0.0519 AC: 2158 AN: 41562

American (AMR) AF: 0.0321 AC: 491 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1309 AN: 5168

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4832

European-Finnish (FIN) AF: 0.0774 AC: 821 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 917 AN: 68038

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0253 Hom.: 714

Bravo AF: 0.0379

TwinsUK AF: 0.0151 AC: 56

ALSPAC AF: 0.0169 AC: 65

ESP6500AA AF: 0.0483 AC: 213

ESP6500EA AF: 0.0126 AC: 108

ExAC AF: 0.0434 AC: 5269

Asia WGS AF: 0.0960 AC: 331 AN: 3478

EpiCase AF: 0.0114

EpiControl AF: 0.0120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0010
DANN	Benign	0.82
DEOGEN2	Benign	0.0027	T;T;.;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.31	.;.;T;T
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;N;.;N
PhyloP100		-2.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.37	N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.42	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.031
MPC		0.0037
ClinPred		0.0027	T
GERP RS		-11
Varity_R		0.015
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs8191613; hg19: chr8-11637276; COSMIC: COSV52706850; COSMIC: COSV52706850;