6-5261612-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006567.5(FARS2):c.-70A>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 0.359 in 152,166 control chromosomes in the GnomAD database, including 11,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11952 hom., cov: 33)
  • Exomes 𝑓: 0.30 (4 hom.)
• Consequence: FARS2 NM_006567.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.675

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-5261612-A-G is Benign according to our data. Variant chr6-5261612-A-G is described in ClinVar as [Benign]. Clinvar id is 1288931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARS2	NM_006567.5	c.-70A>G		5_prime_UTR_variant	1/7	ENST00000274680.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARS2	ENST00000274680.9	c.-70A>G		5_prime_UTR_variant	1/7	1	NM_006567.5	P1
FARS2	ENST00000324331.10	c.-22+254A>G		intron_variant		1		P1
FARS2	ENST00000602691.1	c.-134A>G		5_prime_UTR_variant	1/3	3
FARS2	ENST00000648580.1	c.-70A>G		5_prime_UTR_variant, NMD_transcript_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54576 AN: 151960 Hom.: 11919 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.302 AC: 26 AN: 86 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 24 AN XY: 72

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.359 AC: 54666 AN: 152080 Hom.: 11952 Cov.: 33 AF XY: 0.353 AC XY: 26255 AN XY: 74344

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.354

Alfa AF: 0.247 Hom.: 1563

Bravo AF: 0.384

Asia WGS AF: 0.244 AC: 853 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	5.3
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2753246; hg19: chr6-5261845;