Genetic Variant FDX2:c.307+76T>A (chr19-10315310-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001397406.1(FDX2):c.307+76T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FDX2
NM_001397406.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

5 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

FDX2 links:

ENSG00000167807 (HGNC:):

ENSG00000167807 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FDX2	NM_001397406.1 link	c.307+76T>A	intron_variant	Intron 3 of 4	ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1 link	n.326+76T>A	intron_variant	Intron 3 of 7
FDX2-ZGLP1	NR_176052.1 link	n.387+76T>A	intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FDX2	ENST00000393708.3 link	c.307+76T>A	intron_variant	Intron 3 of 4	1	NM_001397406.1	ENSP00000377311.5
ENSG00000167807	ENST00000452032.6 link	n.307+76T>A	intron_variant	Intron 3 of 10	2		ENSP00000408510.3
ENSG00000267303	ENST00000586529.1 link	n.*1537T>A	downstream_gene_variant		5		ENSP00000467814.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144778

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000160

AC:

AN:

626070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

317872

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

14900

American (AMR)

AF:

0.00

AC:

AN:

17470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14662

East Asian (EAS)

AF:

0.00

AC:

AN:

29368

South Asian (SAS)

AF:

0.00

AC:

AN:

43266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2366

European-Non Finnish (NFE)

AF:

0.00000224

AC:

AN:

446162

Other (OTH)

AF:

0.00

AC:

AN:

30464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

144800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69808

African (AFR)

AF:

0.00

AC:

AN:

39240

American (AMR)

AF:

0.00

AC:

AN:

14372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.00

AC:

AN:

4640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66636

Other (OTH)

AF:

0.00

AC:

AN:

2016

Alfa

AF:

0.00

Hom.:

65660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.1

(source)

DANN

Benign

0.82

PhyloP100

0.13

PromoterAI

-0.0074

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over