Variant chr10-68431874-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001080449.3(DNA2):c.1971G>A(p.Thr657Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 1,608,528 control chromosomes in the GnomAD database, including 2,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 154 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1858 hom. )

Consequence

DNA2
NM_001080449.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0640

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 10-68431874-C-T is Benign according to our data. Variant chr10-68431874-C-T is described in ClinVar as [Benign]. Clinvar id is 257342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.064 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0597 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.1971G>A	p.Thr657Thr	synonymous_variant	13/21	ENST00000358410.8	NP_001073918.2	P51530-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNA2	ENST00000358410.8 linkuse as main transcript	c.1971G>A	p.Thr657Thr	synonymous_variant	13/21	1	NM_001080449.3	ENSP00000351185.3	P51530-1
DNA2	ENST00000551118.6 linkuse as main transcript	c.1971G>A	p.Thr657Thr	synonymous_variant	13/17	5		ENSP00000450393.3	F8VR31
DNA2	ENST00000399179.6 linkuse as main transcript	n.1971G>A		non_coding_transcript_exon_variant	14/22	2		ENSP00000382132.3	P51530-2

Frequencies

GnomAD3 genomes

AF:

0.0376

AC:

5724

AN:

152118

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0509

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0451

AC:

11189

AN:

247872

Hom.:

390

AF XY:

0.0470

AC XY:

6323

AN XY:

134462

show subpopulations

Gnomad AFR exome

AF:

0.00582

Gnomad AMR exome

AF:

0.0273

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0552

Gnomad FIN exome

AF:

0.0610

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0562

GnomAD4 exome

AF:

0.0457

AC:

66586

AN:

1456292

Hom.:

1858

Cov.:

AF XY:

0.0466

AC XY:

33758

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.00630

Gnomad4 AMR exome

AF:

0.0283

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0550

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0478

GnomAD4 genome

AF:

0.0376

AC:

5724

AN:

152236

Hom.:

154

Cov.:

AF XY:

0.0380

AC XY:

2826

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00763

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0516

Gnomad4 FIN

AF:

0.0594

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0450

Hom.:

136

Bravo

AF:

0.0340

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0501

EpiControl

AF:

0.0503

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 08, 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	Jan 14, 2016	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

-0.29

CADD

Benign

2.3

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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