8-11783275-A-G

Variant names:

• chr8-11783275-A-G
• rs8191642
• NM_145043.4:c.564A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145043.4(NEIL2):​c.564A>G​(p.Pro188Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,896 control chromosomes in the GnomAD database, including 40,730 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 0.24 (5166 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35564 hom.)
• Consequence: NEIL2 NM_145043.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.564A>G	p.Pro188Pro	synonymous	Exon 4 of 5	NP_659480.1
	NEIL2	NM_001135746.3		c.564A>G	p.Pro188Pro	synonymous	Exon 4 of 5	NP_001129218.1
	NEIL2	NM_001349442.2		c.564A>G	p.Pro188Pro	synonymous	Exon 5 of 6	NP_001336371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.564A>G	p.Pro188Pro	synonymous	Exon 4 of 5	ENSP00000284503.6
	NEIL2	ENST00000436750.7	TSL:1	c.564A>G	p.Pro188Pro	synonymous	Exon 4 of 5	ENSP00000394023.2
	NEIL2	ENST00000455213.6	TSL:5	c.564A>G	p.Pro188Pro	synonymous	Exon 5 of 6	ENSP00000397538.2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37230 AN: 152056 Hom.: 5154 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.193 AC: 48574 AN: 251394 AF XY: 0.194

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.0151

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.214 AC: 312570 AN: 1461722 Hom.: 35564 Cov.: 35 AF XY: 0.214 AC XY: 155762 AN XY: 727166

African (AFR) AF: 0.376 AC: 12580 AN: 33474

American (AMR) AF: 0.131 AC: 5880 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7573 AN: 26136

East Asian (EAS) AF: 0.0122 AC: 486 AN: 39700

South Asian (SAS) AF: 0.184 AC: 15888 AN: 86256

European-Finnish (FIN) AF: 0.152 AC: 8134 AN: 53420

Middle Eastern (MID) AF: 0.297 AC: 1710 AN: 5766

European-Non Finnish (NFE) AF: 0.222 AC: 246736 AN: 1111858

Other (OTH) AF: 0.225 AC: 13583 AN: 60388

GnomAD4 genome AF: 0.245 AC: 37267 AN: 152174 Hom.: 5166 Cov.: 33 AF XY: 0.238 AC XY: 17700 AN XY: 74382

African (AFR) AF: 0.367 AC: 15241 AN: 41486

American (AMR) AF: 0.189 AC: 2892 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3470

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5184

South Asian (SAS) AF: 0.167 AC: 808 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10608

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14957 AN: 67988

Other (OTH) AF: 0.245 AC: 519 AN: 2116

Alfa AF: 0.204 Hom.: 1025

Bravo AF: 0.252

Asia WGS AF: 0.120 AC: 415 AN: 3478

EpiCase AF: 0.220

EpiControl AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.075
DANN	Benign	0.46
PhyloP100		-2.2
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: rs8191642; hg19: chr8-11640784; COSMIC: COSV105120018;