6-5261448-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000324331.10(FARS2):c.-22+90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,582 control chromosomes in the GnomAD database, including 11,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11812 hom., cov: 33)
  • Exomes 𝑓: 0.19 (10 hom.)
• Consequence: FARS2 ENST00000324331.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

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 -10 ACMG points.

• BP6: Variant 6-5261448-A-G is Benign according to our data. Variant chr6-5261448-A-G is described in ClinVar as [Benign]. Clinvar id is 1291334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARS2	NM_001318872.2	c.-22+90A>G		intron_variant
FARS2	NM_001374878.1	c.-22+57A>G		intron_variant
FARS2	XM_047418086.1	c.-22+11495A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARS2	ENST00000324331.10	c.-22+90A>G		intron_variant		1		P1
FARS2	ENST00000602691.1	c.-298A>G		5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54369 AN: 151798 Hom.: 11779 Cov.: 33

Gnomad AFR AF: 0.615

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: 0.217

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.191 AC: 127 AN: 666 Hom.: 10 Cov.: 0 AF XY: 0.207 AC XY: 96 AN XY: 464

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.358 AC: 54459 AN: 151916 Hom.: 11812 Cov.: 33 AF XY: 0.352 AC XY: 26141 AN XY: 74252

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.352

Alfa AF: 0.312 Hom.: 1108

Bravo AF: 0.382

Asia WGS AF: 0.244 AC: 852 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.2
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2773320; hg19: chr6-5261681;