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):

• 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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOLA3	NM_212552.3	c.259-292_259-291dupAA		intron_variant	Intron 3 of 3	ENST00000327428.10	NP_997717.2
BOLA3	NM_001035505.2	c.170-292_170-291dupAA		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.259-291_259-290insAA		intron_variant	Intron 3 of 3	1	NM_212552.3	ENSP00000331369.5

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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;