8-11786294-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145043.4(NEIL2):c.*21C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,603,630 control chromosomes in the GnomAD database, including 44,663 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 0.25 (4766 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39897 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4	c.*21C>T		3_prime_UTR_variant	5/5	ENST00000284503.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.*21C>T		3_prime_UTR_variant	5/5	2	NM_145043.4	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37662 AN: 151740 Hom.: 4761 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.245

GnomAD3 exomes AF: 0.227 AC: 52524 AN: 231068 Hom.: 5924 AF XY: 0.226 AC XY: 28634 AN XY: 126424

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.232 AC: 337420 AN: 1451772 Hom.: 39897 Cov.: 33 AF XY: 0.232 AC XY: 167654 AN XY: 721808

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.248 AC: 37679 AN: 151858 Hom.: 4766 Cov.: 32 AF XY: 0.245 AC XY: 18211 AN XY: 74216

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.242

Alfa AF: 0.221 Hom.: 3310

Bravo AF: 0.251

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.48
Dann	Benign	0.55

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: rs1534862; hg19: chr8-11643803; COSMIC: COSV52706601; COSMIC: COSV52706601;