8-11786294-C-T

Variant names:

• chr8-11786294-C-T
• rs1534862
• NM_145043.4:c.*21C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.*21C>T		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	c.*21C>T		3_prime_UTR_variant	Exon 5 of 5	2	NM_145043.4	ENSP00000284503.6

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

GnomAD2 exomes AF: 0.227 AC: 52524 AN: 231068 AF XY: 0.226

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 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

African (AFR) AF: 0.321 AC: 10671 AN: 33268

American (AMR) AF: 0.168 AC: 7341 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 7550 AN: 25976

East Asian (EAS) AF: 0.289 AC: 11367 AN: 39340

South Asian (SAS) AF: 0.189 AC: 16102 AN: 85190

European-Finnish (FIN) AF: 0.226 AC: 11769 AN: 51964

Middle Eastern (MID) AF: 0.285 AC: 1319 AN: 4624

European-Non Finnish (NFE) AF: 0.232 AC: 256808 AN: 1107780

Other (OTH) AF: 0.242 AC: 14493 AN: 59930

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

African (AFR) AF: 0.309 AC: 12761 AN: 41360

American (AMR) AF: 0.198 AC: 3019 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1021 AN: 3466

East Asian (EAS) AF: 0.271 AC: 1388 AN: 5130

South Asian (SAS) AF: 0.176 AC: 843 AN: 4802

European-Finnish (FIN) AF: 0.210 AC: 2223 AN: 10566

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.229 AC: 15598 AN: 67970

Other (OTH) AF: 0.242 AC: 508 AN: 2102

Alfa AF: 0.223 Hom.: 3748

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
PhyloP100		-2.3
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: rs1534862; hg19: chr8-11643803; COSMIC: COSV52706601; COSMIC: COSV52706601;