rs8191613

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103W) has been classified as Likely 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

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]

NEIL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.308G>A	p.Arg103Gln	missense_variant	3/5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.308G>A	p.Arg103Gln	missense_variant	3/5	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

GnomAD3 exomes AF: 0.0450 AC: 11202 AN: 249024 Hom.: 742 AF XY: 0.0408 AC XY: 5496 AN XY: 134812

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 SAS exome AF: 0.00673

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

Gnomad4 AFR exome AF: 0.0574

Gnomad4 AMR exome AF: 0.0494

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.00729

Gnomad4 FIN exome AF: 0.0754

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0286

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

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0220 Hom.: 274

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
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

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

LitVar

Other links and lift over

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