2-74135948-CTTTTTTT-CTTTTTTTTT

Variant names:

• chr2-74135948-C-CTT
• rs55654893
• NM_212552.3:c.259-292_259-291dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_212552.3(BOLA3):​c.259-292_259-291dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.046 (337 hom., cov: 0)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489
• Publications: 0 publications found

Genes affected

BOLA3 (HGNC:24415): (bolA family member 3) This gene encodes a protein that plays an essential role in the production of iron-sulfur (Fe-S) clusters for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases, and for the assembly of the mitochondrial respiratory chain complexes. Mutation in this gene has been associated with multiple mitochondrial dysfunctions syndrome-2. Two alternatively spliced transcript variants encoding different isoforms with distinct subcellular localization have been reported for this gene (PMID:21944046). [provided by RefSeq, Dec 2011]

BOLA3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple mitochondrial dysfunctions syndrome 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-74135948-C-CTT is Benign according to our data. Variant chr2-74135948-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1274334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	NM_212552.3	MANE Select	c.259-292_259-291dupAA		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.170-292_170-291dupAA		intron	N/A	NP_001030582.1	Q53S33-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	ENST00000327428.10	TSL:1 MANE Select	c.259-291_259-290insAA		intron	N/A	ENSP00000331369.5	Q53S33-1
	BOLA3	ENST00000295326.4	TSL:1	c.170-291_170-290insAA		intron	N/A	ENSP00000295326.4	Q53S33-2
	BOLA3	ENST00000477685.5	TSL:1	n.410-291_410-290insAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6148 AN: 134606 Hom.: 337 Cov.: 0

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.00786

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0456 AC: 6144 AN: 134592 Hom.: 337 Cov.: 0 AF XY: 0.0469 AC XY: 3012 AN XY: 64254

African (AFR) AF: 0.0752 AC: 2731 AN: 36308

American (AMR) AF: 0.139 AC: 1810 AN: 13058

Ashkenazi Jewish (ASJ) AF: 0.00786 AC: 26 AN: 3306

East Asian (EAS) AF: 0.122 AC: 564 AN: 4628

South Asian (SAS) AF: 0.0170 AC: 70 AN: 4110

European-Finnish (FIN) AF: 0.0111 AC: 75 AN: 6770

Middle Eastern (MID) AF: 0.00394 AC: 1 AN: 254

European-Non Finnish (NFE) AF: 0.0124 AC: 788 AN: 63452

Other (OTH) AF: 0.0424 AC: 78 AN: 1840

Alfa AF: 0.00475 Hom.: 183

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55654893; hg19: chr2-74363075;