Variant 8-11771524-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145043.4(NEIL2):c.77G>C(p.Gly26Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000237 in 1,614,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

NEIL2
NM_145043.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12420532).

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4 linkuse as main transcript	c.77G>C	p.Gly26Ala	missense_variant	2/5	ENST00000284503.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7 linkuse as main transcript	c.77G>C	p.Gly26Ala	missense_variant	2/5	2	NM_145043.4	P1	Q969S2-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251394

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000235

AC:

344

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

177

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000256

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000567

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

High myopia

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0096

T;T;.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.0

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.037

D;D;T;D

Sift4G

Pathogenic

0.0

D;D;T;D

Polyphen

1.0

D;D;.;D

Vest4

0.59

MVP

0.64

MPC

0.016

ClinPred

0.34

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.17

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over