rs8191667

Positions:

• chr8-11786307-C-A
• chr8-11786307-C-G
• chr8-11786307-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145043.4(NEIL2):​c.*34C>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 0.0000665 in 932,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00047 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.*34C>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.*34C>A		3_prime_UTR_variant	5/5	2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.000470 AC: 40 AN: 85024 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00173

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000248

Gnomad OTH AF: 0.00254

GnomAD3 exomes AF: 0.0000511 AC: 11 AN: 215340 Hom.: 0 AF XY: 0.0000509 AC XY: 6 AN XY: 117952

Gnomad AFR exome AF: 0.0000813

Gnomad AMR exome AF: 0.000257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000106

Gnomad OTH exome AF: 0.000184

GnomAD4 exome AF: 0.0000260 AC: 22 AN: 847206 Hom.: 0 Cov.: 21 AF XY: 0.0000332 AC XY: 14 AN XY: 421338

Gnomad4 AFR exome AF: 0.000280

Gnomad4 AMR exome AF: 0.000343

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000154

Gnomad4 OTH exome AF: 0.0000586

GnomAD4 genome AF: 0.000470 AC: 40 AN: 85116 Hom.: 0 Cov.: 23 AF XY: 0.000525 AC XY: 22 AN XY: 41924

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00173

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000248

Gnomad4 OTH AF: 0.00249

Bravo AF: 0.000196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.49

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: rs8191667; hg19: chr8-11643816;