Genetic Variant NM_145043.4:c.212C>G (chr8-11779671-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145043.4(NEIL2):c.212C>G(p.Pro71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NEIL2
NM_145043.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

0 publications found

Variant links:

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]

NEIL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27981097).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEIL2	NM_145043.4	MANE Select	c.212C>G	p.Pro71Arg	missense	Exon 3 of 5	NP_659480.1	Q969S2-1
NEIL2	NM_001135746.3		c.212C>G	p.Pro71Arg	missense	Exon 3 of 5	NP_001129218.1	Q969S2-1
NEIL2	NM_001349442.2		c.212C>G	p.Pro71Arg	missense	Exon 4 of 6	NP_001336371.1	Q969S2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.212C>G	p.Pro71Arg	missense	Exon 3 of 5	ENSP00000284503.6	Q969S2-1
NEIL2	ENST00000436750.7	TSL:1	c.212C>G	p.Pro71Arg	missense	Exon 3 of 5	ENSP00000394023.2	Q969S2-1
NEIL2	ENST00000455213.6	TSL:5	c.212C>G	p.Pro71Arg	missense	Exon 4 of 6	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.35

M_CAP

Benign

0.0069

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.054

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0090

Polyphen

0.85

Vest4

0.33

MutPred

0.39

Loss of glycosylation at P71 (P = 0.0127)

MVP

0.37

MPC

0.013

ClinPred

0.69

GERP RS

2.5

Varity_R

0.098

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over