chr8-11784362-T-C

Variant names:

• chr8-11784362-T-C
• rs6982453
• NM_145043.4:c.688+963T>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.688+963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,162 control chromosomes in the GnomAD database, including 18,939 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 0.50 (18939 hom., cov: 33)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.688+963T>C		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.688+963T>C		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.688+963T>C		intron	N/A	NP_001336371.1	Q969S2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.688+963T>C		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.688+963T>C		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.688+963T>C		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75426 AN: 152044 Hom.: 18935 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.496 AC: 75464 AN: 152162 Hom.: 18939 Cov.: 33 AF XY: 0.496 AC XY: 36916 AN XY: 74402

African (AFR) AF: 0.497 AC: 20620 AN: 41504

American (AMR) AF: 0.501 AC: 7658 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3892 AN: 5178

South Asian (SAS) AF: 0.453 AC: 2186 AN: 4828

European-Finnish (FIN) AF: 0.493 AC: 5227 AN: 10596

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.482 AC: 32742 AN: 67990

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.477 Hom.: 30395

Bravo AF: 0.501

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.057
DANN	Benign	0.58
PhyloP100		-2.1
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: rs6982453; hg19: chr8-11641871;