8-11771610-T-C

Variant names:

• chr8-11771610-T-C
• rs804269
• NM_145043.4:c.138+25T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145043.4(NEIL2):​c.138+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,602,742 control chromosomes in the GnomAD database, including 389,304 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 0.64 (32595 hom., cov: 31)
  • Exomes 𝑓: 0.70 (356709 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 14 publications found

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]

LOC124901888 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.138+25T>C		intron_variant	Intron 2 of 4	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.138+25T>C		intron_variant	Intron 2 of 4	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97627 AN: 151684 Hom.: 32585 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.644

GnomAD2 exomes AF: 0.721 AC: 176442 AN: 244716 AF XY: 0.721

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.835

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.973

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.683

Gnomad OTH exome AF: 0.694

GnomAD4 exome AF: 0.697 AC: 1011603 AN: 1450940 Hom.: 356709 Cov.: 37 AF XY: 0.697 AC XY: 502403 AN XY: 720470

African (AFR) AF: 0.454 AC: 15067 AN: 33174

American (AMR) AF: 0.822 AC: 36292 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 14579 AN: 25670

East Asian (EAS) AF: 0.981 AC: 38713 AN: 39482

South Asian (SAS) AF: 0.754 AC: 64641 AN: 85704

European-Finnish (FIN) AF: 0.743 AC: 39288 AN: 52900

Middle Eastern (MID) AF: 0.568 AC: 3237 AN: 5700

European-Non Finnish (NFE) AF: 0.687 AC: 758889 AN: 1104346

Other (OTH) AF: 0.684 AC: 40897 AN: 59824

GnomAD4 genome AF: 0.643 AC: 97668 AN: 151802 Hom.: 32595 Cov.: 31 AF XY: 0.652 AC XY: 48351 AN XY: 74184

African (AFR) AF: 0.464 AC: 19205 AN: 41372

American (AMR) AF: 0.746 AC: 11408 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1926 AN: 3462

East Asian (EAS) AF: 0.973 AC: 5012 AN: 5152

South Asian (SAS) AF: 0.769 AC: 3704 AN: 4816

European-Finnish (FIN) AF: 0.759 AC: 8003 AN: 10540

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46249 AN: 67878

Other (OTH) AF: 0.649 AC: 1362 AN: 2098

Alfa AF: 0.637 Hom.: 5317

Bravo AF: 0.637

Asia WGS AF: 0.830 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.38
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs804269; hg19: chr8-11629119;