rs10823195

Variant names:

• chr10-68430177-A-G
• rs10823195
• NM_001080449.3:c.2208+259T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080449.3(DNA2):​c.2208+259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,996 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1477 hom., cov: 31)
• Consequence: DNA2 NM_001080449.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-68430177-A-G is Benign according to our data. Variant chr10-68430177-A-G is described in ClinVar as [Benign]. Clinvar id is 671067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNA2	NM_001080449.3	c.2208+259T>C		intron_variant	Intron 14 of 20	ENST00000358410.8	NP_001073918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNA2	ENST00000358410.8	c.2208+259T>C		intron_variant	Intron 14 of 20	1	NM_001080449.3	ENSP00000351185.3
DNA2	ENST00000551118.6	c.1983+1685T>C		intron_variant	Intron 13 of 16	5		ENSP00000450393.3
DNA2	ENST00000440722.2	c.171+259T>C		intron_variant	Intron 1 of 6	1		ENSP00000389713.1
DNA2	ENST00000399179.6	n.*29+259T>C		intron_variant	Intron 15 of 21	2		ENSP00000382132.3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19332 AN: 151878 Hom.: 1460 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.128 AC: 19381 AN: 151996 Hom.: 1477 Cov.: 31 AF XY: 0.127 AC XY: 9421 AN XY: 74302

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0914 Hom.: 864

Bravo AF: 0.133

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.93
CADD	Benign	1.0
DANN	Benign	0.17

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: rs10823195; hg19: chr10-70189934;