2-42350663-T-TAAATACACAC

Position:

• chr2-42350663-T-TAAATACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004718.4(COX7A2L):​c.*555_*556insGTGTGTATTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28678 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: COX7A2L NM_004718.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

Genes affected

COX7A2L (HGNC:2289): (cytochrome c oxidase subunit 7A2 like) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein similar to polypeptides 1 and 2 of subunit VIIa in the C-terminal region, and also highly similar to the mouse Sig81 protein sequence. This gene is expressed in all tissues, and upregulated in a breast cancer cell line after estrogen treatment. It is possible that this gene represents a regulatory subunit of COX and mediates the higher level of energy production in target cells by estrogen. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX7A2L	NM_004718.4	c.*555_*556insGTGTGTATTT		3_prime_UTR_variant	3/3	ENST00000234301.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX7A2L	ENST00000234301.3	c.*555_*556insGTGTGTATTT		3_prime_UTR_variant	3/3	1	NM_004718.4	P1
COX7A2L	ENST00000378669.5	c.*555_*556insGTGTGTATTT		3_prime_UTR_variant	4/4	2		P1
COX7A2L	ENST00000468711.5	c.192+2548_192+2549insGTGTGTATTT		intron_variant		3
COX7A2L	ENST00000482463.5	n.1761_1762insGTGTGTATTT		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92201 AN: 151420 Hom.: 28638 Cov.: 0

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.609 AC: 92299 AN: 151540 Hom.: 28678 Cov.: 0 AF XY: 0.607 AC XY: 44951 AN XY: 74044

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.584

Alfa AF: 0.459 Hom.: 971

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4181; hg19: chr2-42577803;