rs804292

Positions:

• chr8-11786406-G-A
• chr8-11786406-G-C

Variant summary

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

The NM_145043.4(NEIL2):​c.*133G>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 0.78 in 848,968 control chromosomes in the GnomAD database, including 259,984 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 0.78 (46290 hom., cov: 31)
  • Exomes 𝑓: 0.78 (213694 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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 = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.*133G>A		3_prime_UTR_variant	5/5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.*133G>A		3_prime_UTR_variant	5/5	2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118306 AN: 151944 Hom.: 46242 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.775

GnomAD4 exome AF: 0.780 AC: 543547 AN: 696906 Hom.: 213694 Cov.: 9 AF XY: 0.780 AC XY: 285957 AN XY: 366480

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.779 AC: 118415 AN: 152062 Hom.: 46290 Cov.: 31 AF XY: 0.788 AC XY: 58601 AN XY: 74330

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.777

Alfa AF: 0.765 Hom.: 91269

Bravo AF: 0.777

Asia WGS AF: 0.918 AC: 3189 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	0.14
DANN	Benign	0.52

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: rs804292; hg19: chr8-11643915;