rs368835

Positions:

• chr19-10315310-A-G
• chr19-10315310-A-T

Variant summary

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

The ENST00000393708.3(FDX2):​c.307+76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 767,194 control chromosomes in the GnomAD database, including 250,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (51284 hom., cov: 23)
  • Exomes 𝑓: 0.79 (198934 hom.)
• Consequence: FDX2 ENST00000393708.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.125

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=-0.93).
• BP6: Variant 19-10315310-A-G is Benign according to our data. Variant chr19-10315310-A-G is described in ClinVar as [Benign]. Clinvar id is 1262244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDX2	NM_001397406.1	c.307+76T>C		intron_variant		ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1	n.326+76T>C		intron_variant, non_coding_transcript_variant
FDX2-ZGLP1	NR_176052.1	n.387+76T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDX2	ENST00000393708.3	c.307+76T>C		intron_variant		1	NM_001397406.1	ENSP00000377311	P1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 120978 AN: 144602 Hom.: 51281 Cov.: 23

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.856

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.787 AC: 489801 AN: 622570 Hom.: 198934 Cov.: 9 AF XY: 0.787 AC XY: 248555 AN XY: 316024

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.763

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.803

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.837 AC: 120983 AN: 144624 Hom.: 51284 Cov.: 23 AF XY: 0.833 AC XY: 58040 AN XY: 69700

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.839

Alfa AF: 0.845 Hom.: 4857

Bravo AF: 0.839

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	clinical testing	GeneDx	Aug 06, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.5
DANN	Benign	0.77

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: rs368835; hg19: chr19-10425986;