2-98604359-G-GA

Position:

• chr2-98604359-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001008215.3(COA5):​c.100-169dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 587,100 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (10 hom.)
• Consequence: COA5 NM_001008215.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.849

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 -10 ACMG points.

• BP6: Variant 2-98604359-G-GA is Benign according to our data. Variant chr2-98604359-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1317980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1657/151110) while in subpopulation AFR AF= 0.038 (1570/41280). AF 95% confidence interval is 0.0365. There are 27 homozygotes in gnomad4. There are 785 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.100-169dupT		intron_variant		ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.100-169dupT		intron_variant		1	NM_001008215.3	ENSP00000330730.3

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1650 AN: 150994 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00415

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.00965

GnomAD4 exome AF: 0.00236 AC: 1028 AN: 435990 Hom.: 10 Cov.: 5 AF XY: 0.00231 AC XY: 538 AN XY: 232992

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.00133

Gnomad4 EAS exome AF: 0.00109

Gnomad4 SAS exome AF: 0.000610

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.00375

GnomAD4 genome AF: 0.0110 AC: 1657 AN: 151110 Hom.: 27 Cov.: 33 AF XY: 0.0106 AC XY: 785 AN XY: 73808

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.00414

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000591

Gnomad4 OTH AF: 0.00955

Bravo AF: 0.0127

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs200616122; hg19: chr2-99220822;