10-68416402-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080449.3(DNA2):c.3114+307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 152,166 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (454 hom., cov: 31)
• Consequence: DNA2 NM_001080449.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.358

Genes affected

DNA2 (HGNC:2939): (DNA replication helicase/nuclease 2) This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) and Seckel syndrome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-68416402-G-A is Benign according to our data. Variant chr10-68416402-G-A is described in ClinVar as [Benign]. Clinvar id is 683745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNA2	NM_001080449.3	c.3114+307C>T		intron_variant		ENST00000358410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNA2	ENST00000358410.8	c.3114+307C>T		intron_variant		1	NM_001080449.3	P1
DNA2	ENST00000551118.6	c.2402+305C>T		intron_variant		5
DNA2	ENST00000399179.6	c.*935+307C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10160 AN: 152048 Hom.: 454 Cov.: 31

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0709

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0667 AC: 10157 AN: 152166 Hom.: 454 Cov.: 31 AF XY: 0.0645 AC XY: 4799 AN XY: 74390

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0444 Hom.: 41

Bravo AF: 0.0632

Asia WGS AF: 0.0270 AC: 94 AN: 3478

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

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.1
Dann	Benign	0.44

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: rs111333451; hg19: chr10-70176159;