rs6997097

Positions:

• chr8-11786463-T-C

Variant summary

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

The NM_145043.4(NEIL2):​c.*190T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 626,096 control chromosomes in the GnomAD database, including 1,518 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 0.051 (265 hom., cov: 31)
  • Exomes 𝑓: 0.065 (1253 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.*190T>C		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.*190T>C		3_prime_UTR_variant	5/5	2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7725 AN: 152094 Hom.: 266 Cov.: 31

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0533

GnomAD4 exome AF: 0.0655 AC: 31030 AN: 473886 Hom.: 1253 Cov.: 5 AF XY: 0.0683 AC XY: 17091 AN XY: 250274

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.000837

Gnomad4 SAS exome AF: 0.0991

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.0592

GnomAD4 genome AF: 0.0507 AC: 7722 AN: 152210 Hom.: 265 Cov.: 31 AF XY: 0.0507 AC XY: 3770 AN XY: 74406

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0638 Hom.: 140

Bravo AF: 0.0461

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.66

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: rs6997097; hg19: chr8-11643972;