rs368835

Variant names:

• chr19-10315310-A-G
• rs368835
• NM_001397406.1:c.307+76T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001397406.1(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 NM_001397406.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.125
• Publications: 5 publications found

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)

ENSG00000167807 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FDX2	NM_001397406.1	c.307+76T>C		intron_variant	Intron 3 of 4	ENST00000393708.3	NP_001384335.1
FDX2-ZGLP1	NR_176051.1	n.326+76T>C		intron_variant	Intron 3 of 7
FDX2-ZGLP1	NR_176052.1	n.387+76T>C		intron_variant	Intron 3 of 8

Ensembl

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

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

African (AFR) AF: 0.934 AC: 13881 AN: 14862

American (AMR) AF: 0.776 AC: 13460 AN: 17356

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 11427 AN: 14580

East Asian (EAS) AF: 0.464 AC: 13439 AN: 28974

South Asian (SAS) AF: 0.763 AC: 32881 AN: 43122

European-Finnish (FIN) AF: 0.824 AC: 22487 AN: 27284

Middle Eastern (MID) AF: 0.831 AC: 1955 AN: 2354

European-Non Finnish (NFE) AF: 0.803 AC: 356316 AN: 443738

Other (OTH) AF: 0.791 AC: 23955 AN: 30300

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

African (AFR) AF: 0.931 AC: 36520 AN: 39228

American (AMR) AF: 0.792 AC: 11352 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2718 AN: 3428

East Asian (EAS) AF: 0.435 AC: 2126 AN: 4886

South Asian (SAS) AF: 0.768 AC: 3553 AN: 4626

European-Finnish (FIN) AF: 0.841 AC: 7034 AN: 8360

Middle Eastern (MID) AF: 0.854 AC: 239 AN: 280

European-Non Finnish (NFE) AF: 0.828 AC: 55107 AN: 66576

Other (OTH) AF: 0.839 AC: 1690 AN: 2014

Alfa AF: 0.825 Hom.: 65660

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		0.13
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs368835; hg19: chr19-10425986;