8-11787242-A-G

Variant names:

• chr8-11787242-A-G
• rs4639
• NM_145043.4:c.*969A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145043.4(NEIL2):​c.*969A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,548 control chromosomes in the GnomAD database, including 14,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14428 hom., cov: 32)
  • Exomes 𝑓: 0.55 (69 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.914
• 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]

LOC105379243 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-11787242-A-G is Benign according to our data. Variant chr8-11787242-A-G is described in ClinVar as Benign. ClinVar VariationId is 1259689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 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.*969A>G		3_prime_UTR	Exon 5 of 5	NP_659480.1
	NEIL2	NR_146180.2		n.2624A>G		non_coding_transcript_exon	Exon 5 of 5
	NEIL2	NR_146181.2		n.2791A>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.*969A>G		3_prime_UTR	Exon 5 of 5	ENSP00000284503.6
	NEIL2	ENST00000436750.7	TSL:1	c.*969A>G		3_prime_UTR	Exon 5 of 5	ENSP00000394023.2
	NEIL2	ENST00000455213.6	TSL:5	c.*969A>G		3_prime_UTR	Exon 6 of 6	ENSP00000397538.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61165 AN: 151968 Hom.: 14415 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.545 AC: 252 AN: 462 Hom.: 69 Cov.: 0 AF XY: 0.536 AC XY: 149 AN XY: 278

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.553 AC: 238 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.409 AC: 9 AN: 22

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.402 AC: 61191 AN: 152086 Hom.: 14428 Cov.: 32 AF XY: 0.416 AC XY: 30941 AN XY: 74332

African (AFR) AF: 0.170 AC: 7050 AN: 41482

American (AMR) AF: 0.571 AC: 8719 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3466

East Asian (EAS) AF: 0.727 AC: 3764 AN: 5180

South Asian (SAS) AF: 0.587 AC: 2827 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5834 AN: 10564

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30572 AN: 67978

Other (OTH) AF: 0.419 AC: 884 AN: 2112

Alfa AF: 0.422 Hom.: 11833

Bravo AF: 0.393

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31253066)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.59
PhyloP100		0.91
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: rs4639; hg19: chr8-11644751;