8-11771610-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NEIL2	NM_145043.4	c.138+25T>C		intron_variant		ENST00000284503.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.138+25T>C		intron_variant		2	NM_145043.4	P1

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

GnomAD3 exomes AF: 0.721 AC: 176442 AN: 244716 Hom.: 65216 AF XY: 0.721 AC XY: 95518 AN XY: 132568

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 SAS exome AF: 0.756

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

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.743

Gnomad4 NFE exome AF: 0.687

Gnomad4 OTH exome AF: 0.684

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

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.649

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

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

LitVar

Other links and lift over

dbSNP: rs804269; hg19: chr8-11629119;