2-74135948-CTTTTTTT-CTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_212552.3(BOLA3):​c.259-292_259-291delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0027 (3 hom., cov: 0)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Not reported in ClinVar
• 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):

• multiple mitochondrial dysfunctions syndrome 2

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00267 (359/134626) while in subpopulation AFR AF = 0.00476 (173/36356). AF 95% confidence interval is 0.00418. There are 3 homozygotes in GnomAd4. There are 162 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOLA3	NM_212552.3	c.259-292_259-291delAA		intron_variant	Intron 3 of 3	ENST00000327428.10	NP_997717.2
BOLA3	NM_001035505.2	c.170-292_170-291delAA		intron_variant	Intron 2 of 2		NP_001030582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOLA3	ENST00000327428.10	c.259-292_259-291delAA		intron_variant	Intron 3 of 3	1	NM_212552.3	ENSP00000331369.5

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 358 AN: 134642 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

Gnomad ASJ AF: 0.00726

Gnomad EAS AF: 0.00258

Gnomad SAS AF: 0.00121

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00163

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

GnomAD4 genome AF: 0.00267 AC: 359 AN: 134626 Hom.: 3 Cov.: 0 AF XY: 0.00252 AC XY: 162 AN XY: 64272

African (AFR) AF: 0.00476 AC: 173 AN: 36356

American (AMR) AF: 0.00130 AC: 17 AN: 13080

Ashkenazi Jewish (ASJ) AF: 0.00726 AC: 24 AN: 3308

East Asian (EAS) AF: 0.00259 AC: 12 AN: 4636

South Asian (SAS) AF: 0.00122 AC: 5 AN: 4110

European-Finnish (FIN) AF: 0.00414 AC: 28 AN: 6756

Middle Eastern (MID) AF: 0.00787 AC: 2 AN: 254

European-Non Finnish (NFE) AF: 0.00148 AC: 94 AN: 63418

Other (OTH) AF: 0.00217 AC: 4 AN: 1842

Alfa AF: 0.000288 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs55654893; hg19: chr2-74363075;