rs222471

Variant names:

• chr2-42410917-T-C
• rs222471
• ENST00000423797.2:n.398+2782A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000423797.2(COX7A2L):​n.398+2782A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,200 control chromosomes in the GnomAD database, including 1,669 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1669 hom., cov: 32)
• Consequence: COX7A2L ENST00000423797.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

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]

KCNG3 (HGNC:18306): (potassium voltage-gated channel modifier subfamily G member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This member is a gamma subunit functioning as a modulatory molecule. Alternative splicing results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNG3	XR_007069666.1	n.1317+2782A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX7A2L	ENST00000423797.2	n.398+2782A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22200 AN: 152082 Hom.: 1665 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.146 AC: 22220 AN: 152200 Hom.: 1669 Cov.: 32 AF XY: 0.144 AC XY: 10732 AN XY: 74412

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.134

Alfa AF: 0.139 Hom.: 2583

Bravo AF: 0.148

Asia WGS AF: 0.153 AC: 535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs222471; hg19: chr2-42638057;