2-98601088-C-T

Position:

• chr2-98601088-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001008215.3(COA5):​c.184-295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,852 control chromosomes in the GnomAD database, including 5,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5203 hom., cov: 31)
• Consequence: COA5 NM_001008215.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.884

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 2-98601088-C-T is Benign according to our data. Variant chr2-98601088-C-T is described in ClinVar as [Benign]. Clinvar id is 670019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.184-295G>A		intron_variant		ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.184-295G>A		intron_variant		1	NM_001008215.3	ENSP00000330730.3
COA5	ENST00000466848.1	n.161-295G>A		intron_variant		3
COA5	ENST00000480666.1	n.684-295G>A		intron_variant		2
COA5	ENST00000483527.5	n.330-295G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39538 AN: 151734 Hom.: 5191 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.261 AC: 39586 AN: 151852 Hom.: 5203 Cov.: 31 AF XY: 0.259 AC XY: 19250 AN XY: 74230

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.296

Alfa AF: 0.255 Hom.: 604

Bravo AF: 0.265

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-1.0
CADD	Benign	0.56
DANN	Benign	0.56

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: rs7562232; hg19: chr2-99217551;