Variant 8-11786044-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145043.4(NEIL2):c.770G>T(p.Arg257Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,614,080 control chromosomes in the GnomAD database, including 1,531 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.

Frequency

Genomes: 𝑓 0.023 ( 157 hom., cov: 32)

Exomes 𝑓: 0.022 ( 1374 hom. )

Consequence

NEIL2
NM_145043.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Variant links:

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 links:

NEIL2 (HGNC:):

NEIL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047496855).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4 linkuse as main transcript	c.770G>T	p.Arg257Leu	missense_variant	5/5	ENST00000284503.7	NP_659480.1	Q969S2-1A0A024R361

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7 linkuse as main transcript	c.770G>T	p.Arg257Leu	missense_variant	5/5	2	NM_145043.4	ENSP00000284503.6		Q969S2-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3452

AN:

152114

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0381

AC:

9580

AN:

251478

Hom.:

599

AF XY:

0.0355

AC XY:

4822

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.0424

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.00660

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0300

GnomAD4 exome

AF:

0.0217

AC:

31712

AN:

1461848

Hom.:

1374

Cov.:

AF XY:

0.0211

AC XY:

15334

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.0409

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.00719

Gnomad4 FIN exome

AF:

0.0756

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0227

AC:

3449

AN:

152232

Hom.:

157

Cov.:

AF XY:

0.0263

AC XY:

1958

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00448

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0175

Hom.:

171

Bravo

AF:

0.0199

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0364

AC:

4421

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.7

DANN

Benign

0.53

DEOGEN2

Benign

0.014

T;T;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.76

.;.;T;T;T

MetaRNN

Benign

0.0047

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.0

N;N;.;.;N

PrimateAI

Benign

0.34

PROVEAN

Benign

4.7

N;N;N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B

Vest4

0.071

MPC

0.0036

ClinPred

0.0030

GERP RS

3.0

Varity_R

0.062

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over