2-98604244-T-C

Position:

• chr2-98604244-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008215.3(COA5):​c.100-53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,296,498 control chromosomes in the GnomAD database, including 43,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4401 hom., cov: 32)
  • Exomes 𝑓: 0.26 (38687 hom.)
• Consequence: COA5 NM_001008215.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.130

Genes affected

COA5 (HGNC:33848): (cytochrome c oxidase assembly factor 5) This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency, a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to a severe disease affecting several tissues and organs. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-98604244-T-C is Benign according to our data. Variant chr2-98604244-T-C is described in ClinVar as [Benign]. Clinvar id is 673470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.100-53A>G		intron_variant		ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.100-53A>G		intron_variant		1	NM_001008215.3	ENSP00000330730.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35895 AN: 152004 Hom.: 4405 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.257 AC: 293919 AN: 1144376 Hom.: 38687 Cov.: 16 AF XY: 0.259 AC XY: 151302 AN XY: 584600

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.236 AC: 35911 AN: 152122 Hom.: 4401 Cov.: 32 AF XY: 0.235 AC XY: 17497 AN XY: 74372

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.278

Alfa AF: 0.242 Hom.: 564

Bravo AF: 0.238

Asia WGS AF: 0.287 AC: 995 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.9
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs4851144; hg19: chr2-99220707; COSMIC: COSV60831097; COSMIC: COSV60831097;