Variant 10-68415128-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080449.3(DNA2):c.3115-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,454,880 control chromosomes in the GnomAD database, including 10,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1001 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9486 hom. )

Consequence

DNA2
NM_001080449.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.47

Variant links:

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]

DNA2 links:

DNA2 (HGNC:):

DNA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 10-68415128-A-G is Benign according to our data. Variant chr10-68415128-A-G is described in ClinVar as [Benign]. Clinvar id is 1292160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNA2	NM_001080449.3 linkuse as main transcript	c.3115-21T>C		intron_variant		ENST00000358410.8	NP_001073918.2	P51530-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DNA2	ENST00000358410.8 linkuse as main transcript	c.3115-21T>C	intron_variant	1	NM_001080449.3	ENSP00000351185.3	P51530-1
DNA2	ENST00000551118.6 linkuse as main transcript	c.2403-21T>C	intron_variant	5		ENSP00000450393.3	F8VR31
DNA2	ENST00000399179.6 linkuse as main transcript	n.*936-21T>C	intron_variant	2		ENSP00000382132.3	P51530-2

Frequencies

GnomAD3 genomes

AF:

0.0937

AC:

14254

AN:

152066

Hom.:

998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0192

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.0961

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.153

AC:

24868

AN:

162728

Hom.:

2451

AF XY:

0.156

AC XY:

13406

AN XY:

86192

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.0988

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.109

AC:

142459

AN:

1302696

Hom.:

9486

Cov.:

AF XY:

0.113

AC XY:

73368

AN XY:

648214

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.0927

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0937

AC:

14267

AN:

152184

Hom.:

1001

Cov.:

AF XY:

0.0999

AC XY:

7433

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0191

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.0961

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.108

Hom.:

221

Bravo

AF:

0.0906

Asia WGS

AF:

0.177

AC:

618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.9

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over