8-11771620-C-G

Variant names:

• chr8-11771620-C-G
• rs804268
• NM_145043.4:c.138+35C>G

Variant summary

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

The NM_145043.4(NEIL2):​c.138+35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,594,552 control chromosomes in the GnomAD database, including 138,388 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 0.35 (10806 hom., cov: 32)
  • Exomes 𝑓: 0.42 (127582 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 14 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]

LOC124901888 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 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.138+35C>G		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.138+35C>G		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.138+35C>G		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.138+35C>G		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.138+35C>G		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.138+35C>G		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52877 AN: 151836 Hom.: 10801 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.427 AC: 101961 AN: 238618 AF XY: 0.433

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.416 AC: 599782 AN: 1442598 Hom.: 127582 Cov.: 33 AF XY: 0.418 AC XY: 299093 AN XY: 715562

African (AFR) AF: 0.115 AC: 3793 AN: 32996

American (AMR) AF: 0.463 AC: 20131 AN: 43514

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7611 AN: 25158

East Asian (EAS) AF: 0.516 AC: 20355 AN: 39414

South Asian (SAS) AF: 0.486 AC: 41110 AN: 84652

European-Finnish (FIN) AF: 0.463 AC: 24267 AN: 52416

Middle Eastern (MID) AF: 0.321 AC: 1812 AN: 5644

European-Non Finnish (NFE) AF: 0.416 AC: 457255 AN: 1099320

Other (OTH) AF: 0.394 AC: 23448 AN: 59484

GnomAD4 genome AF: 0.348 AC: 52892 AN: 151954 Hom.: 10806 Cov.: 32 AF XY: 0.358 AC XY: 26569 AN XY: 74268

African (AFR) AF: 0.130 AC: 5410 AN: 41504

American (AMR) AF: 0.445 AC: 6797 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2857 AN: 5148

South Asian (SAS) AF: 0.496 AC: 2382 AN: 4806

European-Finnish (FIN) AF: 0.476 AC: 5016 AN: 10540

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28151 AN: 67908

Other (OTH) AF: 0.357 AC: 751 AN: 2104

Alfa AF: 0.295 Hom.: 1268

Bravo AF: 0.337

Asia WGS AF: 0.513 AC: 1781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		-0.30
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: rs804268; hg19: chr8-11629129; COSMIC: COSV52707265;