rs804270

chr8-11770112-G-Cchr8-11770112-G-T

Variant summary

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

The NM_145043.4(NEIL2):c.-226G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,902 control chromosomes in the GnomAD database, including 15,605 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 0.44 (15605 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEIL2 NM_145043.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

LOC124901888 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4	c.-226G>C		5_prime_UTR_variant	1/5	ENST00000284503.7
LOC124901888	XR_007060824.1	n.870C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.-226G>C		5_prime_UTR_variant	1/5	2	NM_145043.4	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66377 AN: 151786 Hom.: 15585 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.430

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.225 AC: 9 AN: 40 Hom.: 1 Cov.: 0 AF XY: 0.233 AC XY: 7 AN XY: 30

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.219

GnomAD4 genome AF: 0.437 AC: 66421 AN: 151902 Hom.: 15605 Cov.: 32 AF XY: 0.451 AC XY: 33478 AN XY: 74210

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.437

Alfa AF: 0.283 Hom.: 716

Bravo AF: 0.436

Asia WGS AF: 0.675 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.65
Dann	Benign	0.59

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: rs804270; hg19: chr8-11627621;