8-11771561-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_145043.4(NEIL2):c.114G>A(p.Gln38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,614,102 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (28 hom.)
• Consequence: NEIL2 NM_145043.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.706

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-11771561-G-A is Benign according to our data. Variant chr8-11771561-G-A is described in ClinVar as [Benign]. Clinvar id is 771875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.706 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00458 (6697/1461818) while in subpopulation MID AF= 0.0217 (125/5758). AF 95% confidence interval is 0.0186. There are 28 homozygotes in gnomad4_exome. There are 3236 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4	c.114G>A	p.Gln38=	synonymous_variant	2/5	ENST00000284503.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.114G>A	p.Gln38=	synonymous_variant	2/5	2	NM_145043.4	P1

Frequencies

GnomAD3 genomes AF: 0.00706 AC: 1075 AN: 152166 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00447 AC: 1122 AN: 250988 Hom.: 3 AF XY: 0.00431 AC XY: 585 AN XY: 135658

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00500

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00458 AC: 6697 AN: 1461818 Hom.: 28 Cov.: 31 AF XY: 0.00445 AC XY: 3236 AN XY: 727204

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00167

Gnomad4 FIN exome AF: 0.000786

Gnomad4 NFE exome AF: 0.00445

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.00710 AC: 1081 AN: 152284 Hom.: 8 Cov.: 32 AF XY: 0.00677 AC XY: 504 AN XY: 74456

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00607 Hom.: 2

Bravo AF: 0.00750

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.2
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs35833462; hg19: chr8-11629070; COSMIC: COSV99462593;