chr10-68471576-C-T

Variant names:

• chr10-68471576-C-T
• rs2281699
• NM_001080449.3:c.74+215G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080449.3(DNA2):​c.74+215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNA2 NM_001080449.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial DNA deletion syndrome with progressive myopathy

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• Seckel syndrome 8

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNA2	NM_001080449.3	c.74+215G>A		intron_variant	Intron 1 of 20	ENST00000358410.8	NP_001073918.2
DNA2	NR_102264.2	n.163+215G>A		intron_variant	Intron 2 of 21
DNA2	XM_006717680.3	c.164+215G>A		intron_variant	Intron 2 of 21		XP_006717743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNA2	ENST00000358410.8	c.74+215G>A		intron_variant	Intron 1 of 20	1	NM_001080449.3	ENSP00000351185.3
DNA2	ENST00000551118.6	c.74+215G>A		intron_variant	Intron 1 of 16	5		ENSP00000450393.3
DNA2	ENST00000399179.6	n.74+215G>A		intron_variant	Intron 2 of 21	2		ENSP00000382132.3
DNA2	ENST00000550357.1	n.74+215G>A		intron_variant	Intron 1 of 3	4		ENSP00000450014.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.94
PhyloP100		-0.060
PromoterAI		-0.050	Neutral

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

Other links and lift over

dbSNP: rs2281699; hg19: chr10-70231333;