rs804267

Positions:

• chr8-11771732-G-A

Variant summary

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

The NM_145043.4(NEIL2):​c.138+147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 742,908 control chromosomes in the GnomAD database, including 172,273 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 (32004 hom., cov: 31)
  • Exomes 𝑓: 0.68 (140269 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.138+147G>A		intron_variant		ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.138+147G>A		intron_variant		2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96776 AN: 151916 Hom.: 31994 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.680 AC: 401792 AN: 590874 Hom.: 140269 AF XY: 0.682 AC XY: 209891 AN XY: 307924

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.975

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.718

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.637 AC: 96817 AN: 152034 Hom.: 32004 Cov.: 31 AF XY: 0.645 AC XY: 47904 AN XY: 74316

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.646

Alfa AF: 0.669 Hom.: 69433

Bravo AF: 0.632

Asia WGS AF: 0.827 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.91

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: rs804267; hg19: chr8-11629241;