Genetic Variant NEIL2:c.-586C>G (chr8-11769752-C-G) – 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.-586C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,396 control chromosomes in the GnomAD database, including 2,294 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 0.15 ( 2285 hom., cov: 33)

Exomes 𝑓: 0.26 ( 9 hom. )

Consequence

NEIL2
NM_145043.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.266

Publications

11 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4 link	c.-586C>G		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.-586C>G		5_prime_UTR_variant	Exon 1 of 5	2	NM_145043.4	ENSP00000284503.6		Q969S2-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22977

AN:

152128

Hom.:

2292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.257

AC:

AN:

152

Hom.:

Cov.:

AF XY:

0.275

AC XY:

AN XY:

120

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.261

AC:

AN:

134

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.151

AC:

22963

AN:

152244

Hom.:

2285

Cov.:

AF XY:

0.143

AC XY:

10647

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0450

AC:

1870

AN:

41564

American (AMR)

AF:

0.130

AC:

1989

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

795

AN:

3472

East Asian (EAS)

AF:

0.00194

AC:

AN:

5162

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4826

European-Finnish (FIN)

AF:

0.129

AC:

1370

AN:

10614

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15502

AN:

67980

Other (OTH)

AF:

0.175

AC:

371

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1013

2027

3040

4054

5067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.0914

Hom.:

135

Bravo

AF:

0.146

Asia WGS

AF:

0.0630

AC:

222

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

-0.27

PromoterAI

-0.23

Neutral

(source)

Mutation Taster

=300/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over