8-11779353-T-C

Variant names:

• chr8-11779353-T-C
• rs804256
• NM_145043.4:c.139-245T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145043.4(NEIL2):​c.139-245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,208 control chromosomes in the GnomAD database, including 7,520 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 0.29 (7520 hom., cov: 31)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.139-245T>C		intron_variant	Intron 2 of 4	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.139-245T>C		intron_variant	Intron 2 of 4	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43939 AN: 152090 Hom.: 7516 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43955 AN: 152208 Hom.: 7520 Cov.: 31 AF XY: 0.294 AC XY: 21905 AN XY: 74408

African (AFR) AF: 0.103 AC: 4272 AN: 41554

American (AMR) AF: 0.371 AC: 5683 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5176

South Asian (SAS) AF: 0.353 AC: 1702 AN: 4822

European-Finnish (FIN) AF: 0.425 AC: 4501 AN: 10584

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24421 AN: 67994

Other (OTH) AF: 0.303 AC: 636 AN: 2102

Alfa AF: 0.320 Hom.: 13478

Bravo AF: 0.277

Asia WGS AF: 0.334 AC: 1164 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	3.3
DANN	Benign	0.53
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs804256; hg19: chr8-11636862;