2-98608437-T-C

Position:

• chr2-98608437-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001008215.3(COA5):​c.-32A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,351,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: COA5 NM_001008215.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.973

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-98608437-T-C is Benign according to our data. Variant chr2-98608437-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 668339.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA5	NM_001008215.3	c.-32A>G		5_prime_UTR_variant	1/3	ENST00000328709.8	NP_001008216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA5	ENST00000328709.8	c.-32A>G		5_prime_UTR_variant	1/3	1	NM_001008215.3	ENSP00000330730.3
COA5	ENST00000409997.1	c.-32A>G		5_prime_UTR_variant	1/3	4		ENSP00000386934.1
COA5	ENST00000483527.5	n.71A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1351084 Hom.: 0 Cov.: 22 AF XY: 0.00000446 AC XY: 3 AN XY: 672046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jun 01, 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	-0.86
CADD	Benign	5.3
DANN	Benign	0.48
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1575226737; hg19: chr2-99224900;