Genetic Variant NEIL2:c.-226G>C (chr8-11770112-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145043.4(NEIL2):c.-226G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,902 control chromosomes in the GnomAD database, including 15,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15605 hom., cov: 32)

Exomes 𝑓: 0.23 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

NEIL2
NM_145043.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

22 publications found

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:

LOC124901888 (HGNC:):

LOC124901888 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4 link	c.-226G>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000284503.7	NP_659480.1	Q969S2-1A0A024R361

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7 link	c.-226G>C		5_prime_UTR_variant	Exon 1 of 5	2	NM_145043.4	ENSP00000284503.6		Q969S2-1

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66377

AN:

151786

Hom.:

15585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.430

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.225

AC:

AN:

Hom.:

Cov.:

AF XY:

0.233

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.219

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.437

AC:

66421

AN:

151902

Hom.:

15605

Cov.:

AF XY:

0.451

AC XY:

33478

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.310

AC:

12858

AN:

41428

American (AMR)

AF:

0.577

AC:

8810

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1076

AN:

3470

East Asian (EAS)

AF:

0.800

AC:

4101

AN:

5128

South Asian (SAS)

AF:

0.563

AC:

2709

AN:

4810

European-Finnish (FIN)

AF:

0.553

AC:

5832

AN:

10552

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29536

AN:

67916

Other (OTH)

AF:

0.437

AC:

923

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1778

3555

5333

7110

8888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.283

Hom.:

716

Bravo

AF:

0.436

Asia WGS

AF:

0.675

AC:

2345

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.65

(source)

DANN

Benign

0.59

PhyloP100

-1.7

PromoterAI

0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over