Genetic Variant NEIL2:c.*190T>C (chr8-11786463-T-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.*190T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 626,096 control chromosomes in the GnomAD database, including 1,518 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 0.051 ( 265 hom., cov: 31)

Exomes 𝑓: 0.065 ( 1253 hom. )

Consequence

NEIL2
NM_145043.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.93

Publications

7 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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4 link	c.*190T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7 link	c.*190T>C		3_prime_UTR_variant	Exon 5 of 5	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7725

AN:

152094

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.0723

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0533

GnomAD4 exome

AF:

0.0655

AC:

31030

AN:

473886

Hom.:

1253

Cov.:

AF XY:

0.0683

AC XY:

17091

AN XY:

250274

show subpopulations

African (AFR)

AF:

0.0145

AC:

188

AN:

12962

American (AMR)

AF:

0.0346

AC:

769

AN:

22252

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

230

AN:

14700

East Asian (EAS)

AF:

0.000837

AC:

AN:

31058

South Asian (SAS)

AF:

0.0991

AC:

4732

AN:

47748

European-Finnish (FIN)

AF:

0.0703

AC:

2225

AN:

31644

Middle Eastern (MID)

AF:

0.0640

AC:

131

AN:

2046

European-Non Finnish (NFE)

AF:

0.0743

AC:

21137

AN:

284600

Other (OTH)

AF:

0.0592

AC:

1592

AN:

26876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

1457

2914

4372

5829

7286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.0507

AC:

7722

AN:

152210

Hom.:

265

Cov.:

AF XY:

0.0507

AC XY:

3770

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0130

AC:

539

AN:

41542

American (AMR)

AF:

0.0385

AC:

589

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3472

East Asian (EAS)

AF:

0.00309

AC:

AN:

5172

South Asian (SAS)

AF:

0.0976

AC:

470

AN:

4814

European-Finnish (FIN)

AF:

0.0723

AC:

766

AN:

10598

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0755

AC:

5137

AN:

68008

Other (OTH)

AF:

0.0527

AC:

111

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

371

743

1114

1486

1857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0606

Hom.:

186

Bravo

AF:

0.0461

Asia WGS

AF:

0.0350

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.1

(source)

DANN

Benign

0.66

PhyloP100

1.9

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

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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