Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001079866.2(BCS1L):c.628G>A(p.Asp210Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,613,996 control chromosomes in the GnomAD database, including 1,415 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. D210D) has been classified as Likely benign.
BCS1L (HGNC:1020): (BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone) This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0016899705).
BP6
Variant 2-218661926-G-A is Benign according to our data. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218661926-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 136502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
not specifiedBenign:2
Mar 21, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
p.Asp210Asn in exon 5 of BCS1L: This variant is not expected to have clinical si gnificance because it has been identified in 23.75% (314/1322) of African chromo somes by the 1000 Genomes Project (Phase 3; dbSNP rs58447305). -
Dec 09, 2011
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Mitochondrial complex III deficiency nuclear type 1Benign:2
Jun 10, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Leigh syndromeBenign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -