19-10310306-G-C

Position:

• chr19-10310306-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001397406.1(FDX2):​c.*180C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 854,504 control chromosomes in the GnomAD database, including 2,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (376 hom., cov: 31)
  • Exomes 𝑓: 0.077 (2347 hom.)
• Consequence: FDX2 NM_001397406.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.614

Genes affected

FDX2 (HGNC:30546): (ferredoxin 2) This gene encodes a member of the ferredoxin family. The encoded protein contains a 2Fe-2S ferredoxin-type domain and is essential for heme A and Fe/S protein biosynthesis. Mutation in FDX1L gene is associated with mitochondrial muscle myopathy. [provided by RefSeq, Sep 2014]

FDX2-ZGLP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-10310306-G-C is Benign according to our data. Variant chr19-10310306-G-C is described in ClinVar as [Benign]. Clinvar id is 1291012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDX2	NM_001397406.1	c.*180C>G		3_prime_UTR_variant	5/5	ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1	n.751C>G		non_coding_transcript_exon_variant	5/8
FDX2-ZGLP1	NR_176052.1	n.812C>G		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDX2	ENST00000393708.3	c.*180C>G		3_prime_UTR_variant	5/5	1	NM_001397406.1	ENSP00000377311	P1
FDX2	ENST00000492239.5	c.*180C>G		3_prime_UTR_variant	4/4	2		ENSP00000488228
FDX2	ENST00000706663.1	c.*60C>G		3_prime_UTR_variant	2/2			ENSP00000516489
FDX2	ENST00000494368.5			downstream_gene_variant		4		ENSP00000467188

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10223 AN: 152122 Hom.: 373 Cov.: 31

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0771 AC: 54123 AN: 702264 Hom.: 2347 Cov.: 9 AF XY: 0.0759 AC XY: 27018 AN XY: 355870

Gnomad4 AFR exome AF: 0.0418

Gnomad4 AMR exome AF: 0.0766

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.0848

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0780

GnomAD4 genome AF: 0.0672 AC: 10229 AN: 152240 Hom.: 376 Cov.: 31 AF XY: 0.0663 AC XY: 4934 AN XY: 74436

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0288

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0243 Hom.: 15

Bravo AF: 0.0678

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs75231016; hg19: chr19-10420982;