dbSNP rs8191667: NEIL2:c.*34C>A (chr8-11786307-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145043.4(NEIL2):c.*34C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 932,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00047 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NEIL2
NM_145043.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL2	NM_145043.4	MANE Select	c.*34C>A	3_prime_UTR	Exon 5 of 5	NP_659480.1	Q969S2-1
NEIL2	NM_001135746.3		c.*34C>A	3_prime_UTR	Exon 5 of 5	NP_001129218.1	Q969S2-1
NEIL2	NM_001349442.2		c.*34C>A	3_prime_UTR	Exon 6 of 6	NP_001336371.1	Q969S2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.*34C>A	3_prime_UTR	Exon 5 of 5	ENSP00000284503.6	Q969S2-1
NEIL2	ENST00000436750.7	TSL:1	c.*34C>A	3_prime_UTR	Exon 5 of 5	ENSP00000394023.2	Q969S2-1
NEIL2	ENST00000455213.6	TSL:5	c.*34C>A	3_prime_UTR	Exon 6 of 6	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes

AF:

0.000470

AC:

AN:

85024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00173

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000248

Gnomad OTH

AF:

0.00254

GnomAD2 exomes

AF:

0.0000511

AC:

AN:

215340

AF XY:

0.0000509

show subpopulations

Gnomad AFR exome

AF:

0.0000813

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000106

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.0000260

AC:

AN:

847206

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

421338

show subpopulations

African (AFR)

AF:

0.000280

AC:

AN:

14286

American (AMR)

AF:

0.000343

AC:

AN:

29114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12938

East Asian (EAS)

AF:

0.000153

AC:

AN:

19628

South Asian (SAS)

AF:

0.00

AC:

AN:

55650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30796

Middle Eastern (MID)

AF:

0.000871

AC:

AN:

2296

European-Non Finnish (NFE)

AF:

0.00000154

AC:

AN:

648340

Other (OTH)

AF:

0.0000586

AC:

AN:

34158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.000470

AC:

AN:

85116

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

41924

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

18816

American (AMR)

AF:

0.00173

AC:

AN:

9826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1730

East Asian (EAS)

AF:

0.00

AC:

AN:

2700

South Asian (SAS)

AF:

0.00

AC:

AN:

3288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.0000248

AC:

AN:

40284

Other (OTH)

AF:

0.00249

AC:

AN:

1206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.37

(source)

DANN

Benign

0.49

PhyloP100

-1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over