10-68415275-CT-C

Variant summary

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

The NM_001080449.3(DNA2):c.3115-169del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 138,712 control chromosomes in the GnomAD database, including 1,262 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1262 hom., cov: 29)
• Consequence: DNA2 NM_001080449.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

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 10-68415275-CT-C is Benign according to our data. Variant chr10-68415275-CT-C is described in ClinVar as [Benign]. Clinvar id is 1273839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNA2	NM_001080449.3	c.3115-169del		intron_variant		ENST00000358410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNA2	ENST00000358410.8	c.3115-169del		intron_variant		1	NM_001080449.3	P1
DNA2	ENST00000551118.6	c.2403-169del		intron_variant		5
DNA2	ENST00000399179.6	c.*936-169del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 18859 AN: 138716 Hom.: 1259 Cov.: 29

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 18871 AN: 138712 Hom.: 1262 Cov.: 29 AF XY: 0.139 AC XY: 9316 AN XY: 67014

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.143

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 12, 2019

- -

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: rs549702509; hg19: chr10-70175032;