2-227325286-C-G

Position:

• chr2-227325286-C-G

Variant summary

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

The NM_001277062.2(MFF):​c.-294C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 149,442 control chromosomes in the GnomAD database, including 37,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (37581 hom., cov: 36)
  • Exomes 𝑓: 0.038 (21 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFF NM_001277062.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

Genes affected

MFF (HGNC:24858): (mitochondrial fission factor) This is a nuclear gene encoding a protein that functions in mitochondrial and peroxisomal fission. The encoded protein recruits dynamin-1-like protein (DNM1L) to mitochondria. There are multiple pseudogenes for this gene on chromosomes 1, 5, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

MFF-DT (HGNC:41067): (MFF divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-227325286-C-G is Benign according to our data. Variant chr2-227325286-C-G is described in ClinVar as [Benign]. Clinvar id is 1259107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-294C>G		5_prime_UTR_variant	1/9	ENST00000304593.14	NP_001263991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14	c.-294C>G		5_prime_UTR_variant	1/9	2	NM_001277062.2	ENSP00000304898	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 105330 AN: 149326 Hom.: 37574 Cov.: 36

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.733

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0376 AC: 73 AN: 1940 Hom.: 21 Cov.: 0 AF XY: 0.0528 AC XY: 58 AN XY: 1098

Gnomad4 AFR exome AF: 0.00602

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0596

Gnomad4 OTH exome AF: 0.00909

GnomAD4 genome AF: 0.705 AC: 105362 AN: 149442 Hom.: 37581 Cov.: 36 AF XY: 0.703 AC XY: 51412 AN XY: 73102

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.737

Alfa AF: 0.646 Hom.: 1630

Asia WGS AF: 0.770 AC: 2676 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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7562498; hg19: chr2-228190002;