10-68414836-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001080449.3(DNA2):c.*202del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 410,064 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: DNA2 NM_001080449.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20

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 10-68414836-TA-T is Benign according to our data. Variant chr10-68414836-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1191352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00352 (536/152334) while in subpopulation AFR AF= 0.0122 (507/41580). AF 95% confidence interval is 0.0113. There are 6 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNA2	NM_001080449.3	c.*202del		3_prime_UTR_variant	21/21	ENST00000358410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNA2	ENST00000358410.8	c.*202del		3_prime_UTR_variant	21/21	1	NM_001080449.3	P1
DNA2	ENST00000551118.6	c.*69del		3_prime_UTR_variant	17/17	5

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 536 AN: 152216 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000458 AC: 118 AN: 257730 Hom.: 1 Cov.: 3 AF XY: 0.000427 AC XY: 56 AN XY: 131228

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.000465

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000642

Gnomad4 OTH exome AF: 0.00127

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152334 Hom.: 6 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74486

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00430

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

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: rs529121415; hg19: chr10-70174593;