Variant 10-68414950-T-A 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 ENST00000551118.6(DNA2):c.2560A>T(p.Met854Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 831,374 control chromosomes in the GnomAD database, including 36,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6149 hom., cov: 32)

Exomes 𝑓: 0.29 ( 30131 hom. )

Consequence

DNA2
ENST00000551118.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.493

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015733242).

BP6

Variant 10-68414950-T-A is Benign according to our data. Variant chr10-68414950-T-A is described in ClinVar as [Benign]. Clinvar id is 1182638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 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.*89A>T		3_prime_UTR_variant	21/21	ENST00000358410.8	NP_001073918.2	P51530-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNA2	ENST00000551118.6 linkuse as main transcript	c.2560A>T	p.Met854Leu	missense_variant	17/17	5		ENSP00000450393.3	F8VR31
DNA2	ENST00000358410 linkuse as main transcript	c.*89A>T		3_prime_UTR_variant	21/21	1	NM_001080449.3	ENSP00000351185.3	P51530-1
DNA2	ENST00000399179.6 linkuse as main transcript	n.*1093A>T		downstream_gene_variant		2		ENSP00000382132.3	P51530-2

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42601

AN:

151878

Hom.:

6146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.294

AC:

199869

AN:

679378

Hom.:

30131

Cov.:

AF XY:

0.290

AC XY:

101519

AN XY:

349936

show subpopulations

Gnomad4 AFR exome

AF:

0.235

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.280

AC:

42607

AN:

151996

Hom.:

6149

Cov.:

AF XY:

0.287

AC XY:

21298

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.218

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.211

Hom.:

583

Bravo

AF:

0.270

TwinsUK

AF:

0.304

AC:

1126

ALSPAC

AF:

0.291

AC:

1121

Asia WGS

AF:

0.191

AC:

667

AN:

3472

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.1

DANN

Benign

0.46

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0016

Vest4

0.27

MVP

0.40

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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