8-11771620-C-G

Position:

• chr8-11771620-C-G

Variant summary

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

The NM_145043.4(NEIL2):​c.138+35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,594,552 control chromosomes in the GnomAD database, including 138,388 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 0.35 (10806 hom., cov: 32)
  • Exomes 𝑓: 0.42 (127582 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.138+35C>G		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+35C>G		intron_variant		2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52877 AN: 151836 Hom.: 10801 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.427 AC: 101961 AN: 238618 Hom.: 22789 AF XY: 0.433 AC XY: 55873 AN XY: 129156

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.549

Gnomad SAS exome AF: 0.493

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.416 AC: 599782 AN: 1442598 Hom.: 127582 Cov.: 33 AF XY: 0.418 AC XY: 299093 AN XY: 715562

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.394

GnomAD4 genome AF: 0.348 AC: 52892 AN: 151954 Hom.: 10806 Cov.: 32 AF XY: 0.358 AC XY: 26569 AN XY: 74268

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.357

Alfa AF: 0.295 Hom.: 1268

Bravo AF: 0.337

Asia WGS AF: 0.513 AC: 1781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.53

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: rs804268; hg19: chr8-11629129; COSMIC: COSV52707265;