rs2326584

Variant names:

• chr6-5288973-G-A
• rs2326584
• NM_006567.5:c.-22+27313G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-5288973-G-A
• chr6-5288973-G-C
• chr6-5288973-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006567.5(FARS2):​c.-22+27313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,138 control chromosomes in the GnomAD database, including 47,932 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 0.79 (47932 hom., cov: 32)
• Consequence: FARS2 NM_006567.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 4 publications found

Genes affected

FARS2 (HGNC:21062): (phenylalanyl-tRNA synthetase 2, mitochondrial) This gene encodes a protein that transfers phenylalanine to its cognate tRNA. This protein localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene can cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

FARS2 Gene-Disease associations (from GenCC):

• metabolic disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• combined oxidative phosphorylation defect type 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 77

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARS2	NM_006567.5	c.-22+27313G>A		intron_variant	Intron 1 of 6	ENST00000274680.9	NP_006558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARS2	ENST00000274680.9	c.-22+27313G>A		intron_variant	Intron 1 of 6	1	NM_006567.5	ENSP00000274680.4
FARS2	ENST00000324331.10	c.-22+27615G>A		intron_variant	Intron 1 of 6	1		ENSP00000316335.5
FARS2	ENST00000602691.1	c.-22+16484G>A		intron_variant	Intron 2 of 2	3		ENSP00000473394.1
FARS2	ENST00000648580.1	n.-22+27313G>A		intron_variant	Intron 1 of 8			ENSP00000497889.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119561 AN: 152022 Hom.: 47870 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.787 AC: 119676 AN: 152138 Hom.: 47932 Cov.: 32 AF XY: 0.787 AC XY: 58531 AN XY: 74368

African (AFR) AF: 0.944 AC: 39213 AN: 41546

American (AMR) AF: 0.727 AC: 11111 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4293 AN: 5170

South Asian (SAS) AF: 0.807 AC: 3879 AN: 4806

European-Finnish (FIN) AF: 0.713 AC: 7528 AN: 10562

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48829 AN: 67976

Other (OTH) AF: 0.761 AC: 1609 AN: 2114

Alfa AF: 0.752 Hom.: 5080

Bravo AF: 0.793

Asia WGS AF: 0.828 AC: 2878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.36
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2326584; hg19: chr6-5289206;