2-74135948-CTTTTTTT-CTTTTTTTT

Variant names:

• chr2-74135948-C-CT
• rs55654893
• NM_212552.3:c.259-291dupA

Variant summary

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

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

• Frequency: Genomes: 𝑓 0.15 (1641 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-CT is Benign according to our data. Variant chr2-74135948-C-CT is described in ClinVar as [Benign]. Clinvar id is 1266728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.147 AC: 19780 AN: 134614 Hom.: 1638 Cov.: 0

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0665

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0935

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.147 AC: 19783 AN: 134602 Hom.: 1641 Cov.: 0 AF XY: 0.147 AC XY: 9464 AN XY: 64256

African (AFR) AF: 0.219 AC: 7946 AN: 36306

American (AMR) AF: 0.162 AC: 2115 AN: 13070

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 220 AN: 3310

East Asian (EAS) AF: 0.155 AC: 719 AN: 4642

South Asian (SAS) AF: 0.186 AC: 763 AN: 4108

European-Finnish (FIN) AF: 0.0517 AC: 350 AN: 6768

Middle Eastern (MID) AF: 0.0945 AC: 24 AN: 254

European-Non Finnish (NFE) AF: 0.113 AC: 7193 AN: 63440

Other (OTH) AF: 0.149 AC: 275 AN: 1842

Alfa AF: 0.0448 Hom.: 183

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 13, 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

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;