10-68415205-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001080449.3(DNA2):c.3115-99del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 500,060 control chromosomes in the GnomAD database, including 10,364 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5033 hom., cov: 24)
  • Exomes 𝑓: 0.21 (5331 hom.)
• Consequence: DNA2 NM_001080449.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436

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 -10 ACMG points.

• BP6: Variant 10-68415205-CA-C is Benign according to our data. Variant chr10-68415205-CA-C is described in ClinVar as [Benign]. Clinvar id is 1278246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNA2	NM_001080449.3	c.3115-99del		intron_variant		ENST00000358410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNA2	ENST00000358410.8	c.3115-99del		intron_variant		1	NM_001080449.3	P1
DNA2	ENST00000551118.6	c.2403-99del		intron_variant		5
DNA2	ENST00000399179.6	c.*936-99del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 34738 AN: 141776 Hom.: 5003 Cov.: 24

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.0487

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.206 AC: 73725 AN: 358208 Hom.: 5331 AF XY: 0.209 AC XY: 38870 AN XY: 186044

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.245 AC: 34820 AN: 141852 Hom.: 5033 Cov.: 24 AF XY: 0.247 AC XY: 16944 AN XY: 68580

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.230

Bravo AF: 0.244

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

Aug 20, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs72035454; hg19: chr10-70174962;