chr8-11771732-G-T

Variant names:

• chr8-11771732-G-T
• rs804267
• NM_145043.4:c.138+147G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145043.4(NEIL2):​c.138+147G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 592,300 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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+147G>T		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.138+147G>T		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.138+147G>T		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+147G>T		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.138+147G>T		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.138+147G>T		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 592300 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 308616

African (AFR) AF: 0.00 AC: 0 AN: 15872

American (AMR) AF: 0.00 AC: 0 AN: 20730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14782

East Asian (EAS) AF: 0.00 AC: 0 AN: 32786

South Asian (SAS) AF: 0.00 AC: 0 AN: 51106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3518

European-Non Finnish (NFE) AF: 0.00000257 AC: 1 AN: 389694

Other (OTH) AF: 0.00 AC: 0 AN: 31058

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.89
PhyloP100		-0.18

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: rs804267; hg19: chr8-11629241;