10-68465747-G-T

Position:

chr10-68465747-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080449.3(DNA2):c.507C>A(p.Ala169Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,604,186 control chromosomes in the GnomAD database, including 50,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7304 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43267 hom. )

Consequence

DNA2
NM_001080449.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.314

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 10-68465747-G-T is Benign according to our data. Variant chr10-68465747-G-T is described in ClinVar as [Benign]. Clinvar id is 257346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.314 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 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.507C>A	p.Ala169Ala	synonymous_variant	4/21	ENST00000358410.8	NP_001073918.2	P51530-1
DNA2	XM_006717680.3 linkuse as main transcript	c.597C>A	p.Ala199Ala	synonymous_variant	5/22		XP_006717743.1
DNA2	XM_017015799.1 linkuse as main transcript	c.-86+2376C>A		intron_variant			XP_016871288.1
DNA2	NR_102264.2 linkuse as main transcript	n.596C>A		non_coding_transcript_exon_variant	5/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNA2	ENST00000358410.8 linkuse as main transcript	c.507C>A	p.Ala169Ala	synonymous_variant	4/21	1	NM_001080449.3	ENSP00000351185.3	P51530-1
DNA2	ENST00000551118.6 linkuse as main transcript	c.507C>A	p.Ala169Ala	synonymous_variant	4/17	5		ENSP00000450393.3	F8VR31
DNA2	ENST00000399179.6 linkuse as main transcript	n.507C>A		non_coding_transcript_exon_variant	5/22	2		ENSP00000382132.3	P51530-2

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44735

AN:

151842

Hom.:

7276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.280

AC:

68446

AN:

244024

Hom.:

10610

AF XY:

0.276

AC XY:

36612

AN XY:

132492

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.233

AC:

338821

AN:

1452228

Hom.:

43267

Cov.:

AF XY:

0.237

AC XY:

171032

AN XY:

722098

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.373

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.295

AC:

44823

AN:

151958

Hom.:

7304

Cov.:

AF XY:

0.296

AC XY:

22008

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.223

Hom.:

3593

Bravo

AF:

0.305

Asia WGS

AF:

0.373

AC:

1295

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -

Seckel syndrome 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Mitochondrial DNA deletion syndrome with progressive myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.1

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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