2-227329854-G-A

Position:

• chr2-227329854-G-A

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.-40-772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 1,059,810 control chromosomes in the GnomAD database, including 453,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57166 hom., cov: 30)
  • Exomes 𝑓: 0.93 (395960 hom.)
• Consequence: MFF NM_001277062.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.93

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-227329854-G-A is Benign according to our data. Variant chr2-227329854-G-A is described in ClinVar as [Benign]. Clinvar id is 1182897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFF	NM_001277062.2	c.-40-772G>A		intron_variant		ENST00000304593.14	NP_001263991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFF	ENST00000304593.14	c.-40-772G>A		intron_variant		2	NM_001277062.2	ENSP00000304898	P1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 130385 AN: 150090 Hom.: 57147 Cov.: 30

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.890

GnomAD4 exome AF: 0.932 AC: 847475 AN: 909618 Hom.: 395960 Cov.: 12 AF XY: 0.933 AC XY: 441694 AN XY: 473220

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.941

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.918

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.914

GnomAD4 genome AF: 0.869 AC: 130446 AN: 150192 Hom.: 57166 Cov.: 30 AF XY: 0.864 AC XY: 63406 AN XY: 73364

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.891

Alfa AF: 0.893 Hom.: 9006

Bravo AF: 0.855

Asia WGS AF: 0.867 AC: 3012 AN: 3474

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.66

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: rs6706656; hg19: chr2-228194570;